A noninferiority trial evaluating the efficacy of bedinvetmab compared to grapiprant for osteoarthritis-pain in dogs using force plate gait analysis

A noninferiority trial evaluating the efficacy of bedinvetmab compared to grapiprant for osteoarthritis-pain in dogs using force plate gait analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A noninferiority trial evaluating the efficacy of bedinvetmab compared to grapiprant for osteoarthritis-pain in dogs using force plate gait analysis Masataka Enomoto, Lauren Buslinger, Connor Thonen-Fleck, Rubia Tomacheuski, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7303674/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Feb, 2026 Read the published version in Scientific Reports → Version 1 posted 14 You are reading this latest preprint version Abstract A randomized, double-blinded, non-inferiority study was conducted to evaluate efficacy of bedinvetmab compared to grapiprant using objective force plate gait analysis (FPGA). Thirty-two eligible dogs (> 20 kg, ≥ 1 year-old) with osteoarthritis (OA) exclusively at hips and/or stifles were randomized 1:1 to the licensed dose of monthly subcutaneous (SC) bedinvetmab (plus daily oral placebo) or daily oral grapiprant (plus monthly SC saline) beginning on day 0 (D0). FPGA and client-reported outcome measures (CROMs) were collected at screening, D0, and every 14 days for 2 months. Based on published FPGA parameters, success-failure rates were calculated for each group. A non-inferiority margin of 21.25% at D42 was defined a priori. FPGA treatment success rate at D42 was 68.8% for bedinvetmab and 56.3% for grapiprant, with the difference being 12.5% (90% confidence interval = -37.5, 18.8). Given that the upper bound of this interval (18.8%) was less than the pre-specified non-inferiority margin of 21.25%, bedinvetmab was concluded to be non-inferior to grapiprant. Overall, pain and associated clinical signs were significantly improved after both treatments based on CROMs. Adverse events were in line with respective label expectations. These data support both bedinvetmab and grapiprant are appropriate first-line treatments for OA pain in dogs. Health sciences/Diseases Health sciences/Health care Health sciences/Medical research bedinvetmab grapiprant canis familiaris osteoarthritis gait analysis noninferiority pain management Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Osteoarthritis (OA) is a degenerative joint disease, often resulting in chronic pain and disability. It is a highly prevalent condition, with an estimated 20–37% of dogs over the age of 1 year affected 1 . Additionally, a recent study found that approximately 40% of young dogs, aged 8 months to 4 years, showed radiographic signs of osteoarthritis (rOA) in one or more appendicular joints. Among these, 40–60% of dogs with rOA had clinical signs in the affected joints, depending on the criteria used to define joint pain 2 . The primary goal of OA pain management is to alleviate discomfort and improve quality of life (QoL). Non-steroidal anti-inflammatory drugs (NSAIDs) were the standard and only pharmacological therapy with robust evidence of efficacy until recently. However, the recent approval of a novel class of analgesic, bedinvetmab (Librela™), has provided an alternative first line treatment option 3 – 6 . Bedinvetmab, a fully canine monoclonal antibody, targets nerve growth factor (NGF), which is a key mediator of OA pain signaling in dogs. It has been licensed in over 50 countries, including the United States, Canada, Europe, the United Kingdom, Latin America, Asia, and Australia. Current pain management guidelines, including those from AAHA, WSAVA, and COAST, recommend both NSAIDs and anti-NGF monoclonal antibodies as appropriate first-line treatments for dogs with OA pain 7 – 9 . However, while clinical studies have demonstrated bedinvetmab's efficacy using subjective outcome measures 3 – 6 , its effectiveness has not yet been evaluated with objective measures such as force plate gait analysis (FPGA). FPGA measures limb use by measuring ground reaction forces (GRFs), and limb use is decreased in the presence of joint pain. FPGA has been used in studies for evaluation of the efficacy of analgesics for OA-related joint pain in dogs 10 , 11 . Accordingly, this study was designed to assess the efficacy of bedinvetmab in comparison to that of grapiprant for the management of pain in dogs with naturally occurring OA as measured using objective gait analysis over a 2-month period. The authors hypothesized that bedinvetmab would be non-inferior to grapiprant based on improvement in objectively measured GRFs. Results As a result of advertising, 211 inquiries were received, and 89 dogs were screened (Fig. 1 ). Thirty-seven dogs received study drug, however, 3 dogs dropped out of the study prior to day 42; [due to diarrhea associated with dietary change (n = 1), unable to collect FPGA due to overlapping strikes (n = 1), and acute forelimb lameness due to recurrent tendinitis (n = 1)], and these dogs were replaced; none of these events were considered to be related to study drug. Additionally, 2 dogs were excluded from analysis due to significant protocol deviation (1 dog in bedinvetmab group did not receive oral medication (placebo) for 2 weeks, 1 dog in grapiprant group was unable to perform force plate gait analysis within the targeted velocity on day 42). Collectively, a total of 32 dogs remained for analysis: 13 different pure breeds in total across 19 dogs; the remaining 13 dogs were mixed breeds. The most common pure breeds were Golden Retriever (n = 5), and Labrador Retriever (n = 3). (Table 1 ). Three dogs dropped out of the study after day 42, 1 dog in the bedinvetmab group (cruciate ligament rupture) and 2 dogs in grapiprant group (cruciate ligament rupture or gastrointestinal issues). Data were not collected from one dog in the grapiprant group at day 14 due to an owner health issue. At screening, body weight was significantly lower in the grapiprant group compared to the bedinvetmab group (p = 0.04). However, there were no significant differences in age, body condition score (BCS), radiographic score, and Canine OsteoArthritis Staging Tool (COAST) between groups. Overall compliance for daily medication was excellent, and 96.4% of placebo/grapiprant prescribed was utilized. Table 2 Demographics of enrolled dogs at screening visit. (mean ± SD and range) Demographic Groups Bedinvetmab (n = 16) Grapiprant (n = 16) Total (n = 32) Age (years) 6.5 ± 3.7 (1.3–13.1) 7.8 ± 2.1 (3.5–12.4) 7.2 ± 3.0 (1.3–13.1) Body weight (kg) 36.3 ± 9.1 (21.3–52.4) 30.0 ± 7.3 (20.2–46.0) 33.1 ± 8.7 (20.2–52.4) Body condition score (scale, 1–9) 5.4 ± 1.0 (4–7) 5.1 ± 0.9 (4–7) 5.3 ± 1.0 (4–7) Sex Male 1M, 12 CM 1 M, 6CM 2M, 18CM Female 3SF 1F, 8SF 1F, 11SF Total radiographic score (0-200) 21.2 ± 11.9 (4–44) 17.2 ± 9.4 (3–35) 19.2 ± 10.8 (3–44) COAST (0–4) 3.7 ± 0.5 (3–4) 3.9 ± 0.3 (3–4) 3.8 ± 0.4 (3–4) M: intact male, F: intact female, CM: castrated male, SF: spayed female, COAST: Canine OsteoArthritis Staging Tool Force plate gait analysis Day 42 (primary endpoint timepoint) On day 42, the peak vertical force (PVF) treatment success rate was 68.8% [95% confidence interval (CI) = 41.3–89.0] for bedinvetmab and 56.3% (95%CI = 29.9–80.2) for grapiprant (Table 3 ). The difference in success rate between the two groups (grapiprant - bedinvetmab) was − 12.5% with the two-sided 90%CI for the difference between the two proportions of -37.5–18.8%. Given that the upper bound of this interval (18.8%) is less than the pre-specified non-inferiority margin of 21.25%, bedinvetmab was concluded to be non-inferior to grapiprant. Furthermore, the p-value for evaluating whether the difference in success rates between the two groups was less than the pre-specified margin of 21.25% was < 0.05, meeting the conventional threshold for statistical significance and further supporting the conclusion of non-inferiority. The day 42 mean ± SD percent increase in PVF and vertical impulse (VI), respectively, compared to day 0 was 7.5 ± 6.8% and 4.3 ± 10.5% for the bedinvetmab group and 6.0 ± 8.7% and 6.5 ± 12.1% for the grapiprant group (both variables significant for both groups, p < 0.001).). (Table 4 ) Changes over time Overall, a significant improvement was seen in PVF and VI in both bedinvetmab and grapiprant groups compared to baseline (day 0 prior to treatment) (Tables 5 and 6 , and Figs. 2 and 3 , P < 0.001). The mean percent change from baseline in PVF was 7.6% (3.8% bodyweight) for the bedinvetmab group and 6.9% (3.9% bodyweight) for the grapiprant group throughout the study (Table 4 ). At all-time points, the mean change in PVF exceeded the suggested threshold (3.5% change from baseline) for clinical significance. The mean percent change from baseline in VI was 5.8% for the bedinvetmab group and 5.7% for the grapiprant group. The mean change in VI also surpassed the threshold at all time points, except on day 14 in the grapiprant group. Table 3 Success rate and 95% confidence interval (CI) for treatment success, defined as an increase of ≥ 3.5% from baseline in peak vertical force (PVF). n: number of dogs Timepoint Group Animals (n) Successes (n) Success (%) CI for success Day 14 Bedinvetmab 16 11 68.8% 41.3%, 89.0% Grapiprant 15 10 66.7% 38.4%, 88.2% Day 28 Bedinvetmab 16 12 75.0% 47.6%, 92.7% Grapiprant 16 9 56.3% 29.9%, 80.2% Day 42 Bedinvetmab 16 11 68.8% 41.3%, 89.0% Grapiprant 16 9 56.3% 29.9%, 80.2% Day 56 Bedinvetmab 15 10 66.7% 38.4%, 88.2% Grapiprant 14 11 78.6% 49.2%, 95.3% Overall Bedinvetmab 69.8% 66.2%, 73.3% Grapiprant 64.5% 54.1%, 74.9% Table 4 Mean change (± SD (range)) from baseline in PVF and VI expressed as a percentage of baseline value. n: number of dogs. PVF: peak vertical force, VI: vertical impulse Timepoint Variables Bedinvetmab Grapiprant n Mean ± SD (range): % n Mean ± SD (range): % Day 14 PVF 16 8.14 ± 8.49 (-2.26, 27.01) 15 5.03 ± 6.60 (-6.51, 16.2) VI 16 7.10 ± 10.70 (-7.55, 24.61) 15 3.51 ± 10.05 (-14.15, 33.55) Day 28 PVF 16 7.03 ± 6.55 (-3.12, 20.82) 16 6.50 ± 6.46 (-1.78, 19.40) VI 16 5.24 ± 8.07 (-4.37, 20.50) 16 4.21 ± 9.86 (-8.50, 25.4) Day 42 PVF 16 7.54 ± 7.03 (-4.22, 17.57) 16 6.03 ± 8.77 (-4.94, 24.72) VI 16 4.28 ± 10.31 (-7.03, 27.34) 16 6.51 ± 11.33 (-11.44, 34.98) Day 56 PVF 15 7.87 ± 8.84 (-5.46, 24.77) 14 10.19 ± 9.83 (-3.26, 30.46) VI 15 6.65 ± 11.45 (-11.85, 27.81) 14 8.59 ± 11.44 (-3.61, 39.80) Overall PVF 7.64 ± 7.54 6.86 ± 7.97 VI 5.80 ± 9.94 5.65 ± 10.53 Table 5 Mean (± SD (range) PVF) and VI expressed as a percentage of bodyweight (BW). n: number of dogs, PVF: peak vertical force, VI: vertical impulse Timepoint Variables Bedinvetmab Grapiprant n Mean ± SD (range): %BW n Mean ± SD (range): %BW Screening PVF 16 60.44 ± 12.56 (26.28, 77.26) 16 60.50 ± 11.40 (38.27, 77.43) VI 16 8.29 ± 1.44 (4.27, 10.95) 16 7.76 ± 1.73 (4.71, 10.46) Day 0 PVF 16 60.25 ± 12.20 (24.57, 77.46) 16 61.40 ± 11.29 (39.48, 79.91) VI 16 8.31 ± 1.55 (3.94, 10.84) 16 8.06 ± 1.61 (5.52, 10.44) Day 14 PVF 16 64.43 ± 11.08 (31.20, 80.46) 15 63.88 ± 9.53 (42.52, 77.44) VI 16 8.81 ± 1.41 (4.91, 10.97) 15 8.13 ± 1.28 (5.68, 10.08) Day 28 PVF 16 83.96 ± 11.48 (29.68, 75.05) 16 65.16 ± 11.30 (41.00, 83.97) VI 16 8.69 ± 1.43 (4.53, 10.81) 16 8.33 ± 1.45 (5.40, 10.41) Day 42 PVF 16 64.41 ± 11.75 (27.05, 76.03) 16 64.45 ± 8.92 (43.50, 78.44) VI 16 8.62 ± 1.49 (4.00, 10.57) 16 8.50 ± 1.57 (5.42, 12.01) Day 56 PVF 15 67.13 ± 6.72 (54.10, 80.68) 14 67.21 ± 9.25 (49.87, 79.21) VI 15 9.12 ± 0.97 (6.77, 10.30) 14 8.53 ± 1.39 (5.74, 10.85) Table 6 Mean change (± SD (range)) from baseline in PVF and VI expressed as a percentage of bodyweight (BW). n: number of dogs. PVF: peak vertical force, VI: vertical impulse Timepoint Variables Bedinvetmab Grapiprant n Mean ± SD (range): %BW n Mean ± SD (range): %BW Day 14 PVF 16 4.17 ± 3.56 (-1.57, 9.46) 15 2.55 ± 4.17 (-5.20, 9.03) VI 16 0.50 ± 0.81 (-0.70, 2.0) 15 0.18 ± 0.72 (-1.4, 1.9) Day 28 PVF 16 3.71 ± 3.30 (-2.42, 9.56) 16 3.76 ± 4.05 (-1.22-13.24) VI 16 0.37 ± 0.58 (-0.4, 1.7) 16 0.27 ± 0.6 (-0.65, 1.47) Day 42 PVF 16 4.16 ± 4.08 (-2.83, 11.36) 16 3.05 ± 4.85 (-3.95, 13.78) VI 16 0.30 ± 0.88 (-0.80, 2.3) 16 0.45 ± 0.91 (-1.12, 2.30) Day 56 PVF 15 4.50 ± 5.70 (-4.23, 16.02) 14 5.50 ± 4.78 (-2.24, 16.98) VI 15 0.51 ± 0.93 (-1.1, 2.0) 14 0.59 ± 0.69 (-0.35, 2.29) Client-reported outcome measures (CROMs) At baseline, there was a significant difference in the Canine Brief Pain Inventory (CBPI) QOL and Sleep and Nighttime Restlessness Evaluation Score Questionnaire (SNoRE) version 3.0 between groups, with the bedinvetmab group having worse scores than the grapiprant group (Supplemental files 1 and 2). Overall, pain and associated clinical signs were significantly improved in both groups after treatment for all CROMs (p < 0.001). Although no significant differences in any CROMs were observed between the groups after treatment, generally numerically greater improvement was seen in the bedinvetmab group than the grapiprant group (Tables 7 and 8 , and Fig. 4 ). Using minimally clinically important difference (MCID) values [reduction of ≥ 4 from baseline in Liverpool Osteoarthritis in Dogs (LOAD)], the treatment success for the bedinvetmab group was 75% and for the grapiprant group was 56.3% at day 42. Seven dogs enrolled in the study had CBPI pain severity score (PSS) < 2 and/or pain interference score (PIS) < 2 at day 0 (3 dogs in bedinvetmab and 4 dogs in grapiprant groups). When only dogs that had CBPI PSS ≥ 2 and PIS ≥ 2 at day 0 were included, our results showed a success rate of 61.5% for bedinvetmab and 46.2% for grapiprant at day 42 (Supplemental file 3). Both groups showed continued improvement over time based on Patient Global Impression of Change (PGIC, supplemental file 4). Overall, a higher proportion of dogs were rated as 'very much improved' or 'much improved' in the bedinvetmab group (62.0%) compared to the grapiprant group (41.0%). Although this difference was not statistically significant, the bedinvetmab group showed a greater overall improvement than the grapiprant group. Table 7 Mean LOAD ± SD (range) and mean change from baseline in LOAD ± SD (range) at each timepoint. n: number of dogs, LOAD: Liverpool Osteoarthritis in Dogs. Time point Group n Mean ± SD (range) Mean change from baseline ± SD (range) Screen Bedinvetmab 16 21.81 ± 6.42 (10, 31) Grapiprant 16 22.00 ± 5.34 (12, 33) Day 0 Bedinvetmab 16 23.69 ± 6.44 (13, 35) Grapiprant 16 21.25 ± 6.60 (11, 39) Day 14 Bedinvetmab 16 17.75 ± 5.15 (8, 27) -5.94 ± 5.07 (-17, 3) Grapiprant 15 17.07 ± 5.73 (6, 27) -3.00 ± 5.67 (-14, 4) Day 28 Bedinvetmab 16 14.88 ± 4.27 (9, 23) -8.81 ± 5.96 (-23, 0) Grapiprant 16 16.38 ± 6.49 (1, 28) -4.88 ± 6.15 (-19, 3) Day 42 Bedinvetmab 16 14.38 ± 6.71 (6, 33) -9.31 ± 7.40 (-25, 3) Grapiprant 16 16.19 ± 6.92 (1, 30) -5.06 ± 6.18 (-19, 3) Day 56 Bedinvetmab 15 12.47 ± 6.00 (5, 28) -10.47 ± 6.97 (-25, -1) Grapiprant 14 15.50 ± 7.73 (1, 31) -6.14 ± 7.15 (-19, 7) Table 8 Success rate and 95% confidence interval (CI) for treatment success, defined as an increase of ≥ 4 from day 0 in LOAD. n: number of dogs, Liverpool Osteoarthritis in Dogs. Time point Group Animals (n) Successes (n) Success (%) CI for success 14 Bedinvetmab 16 12 75.0% 47.6%, 92.7% Grapiprant 15 5 33.3% 11.8%, 61.6% 28 Bedinvetmab 16 13 81.3% 54.4%, 96.0% Grapiprant 16 10 62.5% 35.4%, 84.8% 42 Bedinvetmab 16 12 75.0% 47.6%, 92.7% Grapiprant 16 9 56.3% 29.9%, 80.2% 56 Bedinvetmab 15 13 86.7% 59.5%, 98.3% Grapiprant 14 9 64.3% 35.1%, 87.2% Overall Bedinvetmab 79.5% 74.1%, 85.0% Grapiprant 54.1% 40.1%, 68.1% Other assessments The veterinarian-assessed index joint pain score significantly decreased irrespective of group over time (P = 0.039). Static body weight distribution data also showed a significant improvement in both groups at day 56 compared to baseline and day 28. (Supplemental file 5) Safety assessments Blood work and urinalysis were performed at screening and every month after treatment. Overall, there were no clinically meaningful differences between the groups at the start of the study, and no clinically meaningful changes over time within or between the groups. A statistically significant difference in mean platelet volume (MPV) was observed between the groups at the screening visit, with the bedinvetmab group showing higher values than the grapiprant group. However, mean MPV values in both groups remained within the reference range. Three dogs in the bedinvetmab group and one dog in the grapiprant group had MPV values exceeding the reference range at screening. Phosphorus was significantly lower after treatment compared to baseline in the grapiprant group, although the mean values at those time points stayed within the reference range (supplemental file 6). Adverse events (AEs) were in line with respective label expectations. Although some occurred at higher frequency in one group or the other, the incidence of AEs was similar between the bedinvetmab and grapiprant groups. One or more adverse events occurred in 7/16 dogs in the bedinvetmab group and 8/16 dogs in the grapiprant group (Table 9 ). The most common category of AEs involved skin and appendages in the bedinvetmab group and digestive tract disorders in the grapiprant group. Three musculoskeletal AEs were observed; one dog in each treatment group developed a cruciate ligament rupture contralateral to the index limb diagnosed on day 56; in addition, one dog in the bedinvetmab group had mild transient unilateral forelimb lameness before the day 14 visit that resolved without treatment. For both groups, most AEs were mild and unlikely to be related to investigational drug. In addition to management of the cruciate ligament ruptures, two dogs in the bedinvetmab group received a short course of antibiotics for dermatitis (which resolved by the following visit), one dog in the grapiprant group was treated with antibiotics for a subclinical lower urinary tract infection (resolved within a week) and one dog in the grapiprant group received probiotics for diarrhea (which resolved within several days). Table 9 All adverse events (AEs) following treatment with bedinvetmab or grapiprant. Data are presented as n (%); n: number of dogs (all animals enrolled). Please note that some dogs had multiple adverse events. Systemic organ class clinical signs (VeDDRA) Group Bedinvetmab (n = 16) Grapiprant (n = 16) Total number of AEs 12 11 Skin and appendage disorders 4 1 Renal and urinary disorders 1 1 Digestive tract disorders 3 3 Ear and labyrinth disorders 1 2 Musculoskeletal disorders 2 1 Behavioral disorders 0 2 Eye disorders 0 1 Oral cavity disorders 1 0 Discussion This study demonstrated bedinvetmab was non-inferior to grapiprant based on treatment success for an increase in peak vertical force (PVF) in the index limb during force plate gait analysis (FPGA) on day 42, thus meeting the primary efficacy endpoint. Both groups showed significant improvement from the baseline in objective and subjective outcome measures. Although not statistically significant, numerically greater improvement was observed in the bedinvetmab group compared to the grapiprant group in client-reported outcome measures (CROMs). These findings support the efficacy of bedinvetmab for managing osteoarthritis-associated pain in dogs. At screening, there was a statistically significant difference between the two groups with respect to body weight. Body weight is a well-known factor influencing force plate data, and previous studies demonstrated that PVF and vertical impulse (VI) have strong positive correlations with body weight 12 , 13 . In this study, ground reaction forces were normalized to body weight to minimize its impact and ensure accurate interpretation, as suggested 14 . Gait analysis has been validated as an objective measure of changes in limb use as it relates to joint pain in dogs. 10 , 14 , 15 In particular, the PVF and the VI are commonly used to determine efficacy of therapeutics in OA studies of dogs. 14 A recent review paper suggested that a change from baseline in both PVF and VI over a short time period (less than 6 months) of 3.5% of baseline values (equivalent to 2% bodyweight change from baseline in the index hindlimb) is the minimum value that should be considered clinically important. 14 In the current study, the mean percent change from baseline in PVF and VI exceeded the suggested threshold for clinical significance at all time points, except for VI on day 14 in the grapiprant group. In previously published studies, the actual change from baseline in PVF was measured after six weeks of NSAIDs treatment in dogs with hip OA 16 , 17 . The findings in the current study were comparable to these previous studies 16 , 17 . Overall, the GRF data from the current study indicates that both bedinvetmab and grapiprant are effective treatment options for OA in dogs. Static weight bearing distribution has also been used to evaluate therapeutic efficacy. A significant improvement was observed in both groups on day 56 compared to baseline and day 28. Unlike dynamic assessments such as force plate gait analysis, no immediate improvement was noted. This may be due to the time required to normalize posture following long-term postural adaptations. CBPI, LOAD, Client Specific Outcome Measure (CSOM), and SNoRE have been validated as subjective measures to assess pain and/or clinical signs associated with OA in dogs. 11 , 18 – 20 To evaluate the efficacy of new analgesics, two analytical methods have been commonly used; reduction of pain/disability scores from baseline and binary outcome (success/failure). 11,19,21,22 Overall, pain and associated clinical signs were significantly improved after treatment based on CROMs. Although the study did not include a placebo control group, the degree of improvement observed was comparable to results reported in previous studies 4 , 10 , 23 – 25 . In a prior comparator study evaluating mavacoxib versus meloxicam, the mean reduction in LOAD scores from baseline at week 6 (day 42) ranged from 3.8 to 4.3. Similarly, the mean decreases in CBPI PSS and PIS at week 6 ranged from 0.85 to 1.38 and 1.44 to 1.45, respectively. Grapiprant produced similar improvements in our study as shown in Table 7 and supplemental file 2, while bedinvetmab showed greater improvement with a mean reduction in LOAD of 9.31, a decrease in CBPI PSS of 2.06, and a reduction in CBPI PIS of 2.53. Binary outcome (e.g. success/failure designation) thresholds have been suggested for CBPI and LOAD changes over time. 21 , 22 For CBPI, treatment success and failure have been defined, and the success was considered as a reduction of ≥ 1 in PSS and ≥ 2 in PIS. 21 More recently, a reduction of ≥ 4 in LOAD was suggested as minimal clinically important differences. 22 When analyzing only the subset of dogs with baseline CBPI PSS ≥ 2 and PIS ≥ 2, our results showed a success rate of 61.5% for bedinvetmab and 38.4% for grapiprant at Day 28. These outcomes are in line with previously published placebo-controlled studies where Day 28 CBPI success rates were 43.5% and 47.4% for bedinvetmab 3 ,4 and 48.1% for grapiprant. On day 14, dogs treated with bedinvetmab showed a mean reduction in LOAD scores of 5.94, surpassing the MCID of 4. In contrast, the grapiprant group had a mean reduction of 3.00, which did not reach the MCID. Both groups continued to show further improvement over the course of the study, with total mean reductions of 8.6 points for bedinvetmab and 4.8 points for grapiprant. The mean success rate for bedinvetmab group was 79.5% and for grapiprant group was 54.1%. The PGIC is an anchor-based questionnaire primarily used to assess global changes based on the owner's perception of how much their dog has improved compared to before treatment 26 , 27 . The CROMs quantify changes in specific symptoms or indicators (e.g., pain intensity, functional ability) while the PGIC provides global perspective on overall improvement. Importantly, a statistically significant reduction in a dog’s pain score compared to placebo may not translate into observable improvements in behavior or activity at home. If the PGIC does not indicate a clear and meaningful improvement, statistical significance of other outcome measures may be questioned 28 . Therefore, the PGIC serves as a crucial complement to CROMs, helping to ensure that treatment effects are both statistically valid and clinically meaningful 29 . Both treatment groups demonstrated progressive improvement over the duration of the trial, as measured by the PGIC. However, overall, a higher proportion of dogs were rated as 'very much improved' or 'much improved' in the bedinvetmab group (62.0%) compared to the grapiprant group (41.0%). The joint pain score of the index joint significantly decreased over 2 months of the study period following the treatment. Our assumption is that this was due to treatment, however, it is important to remember that none of the joint pain scoring systems, including ours, have been sufficiently validated. Additionally, the examiner was aware that all dogs received active treatment, which may have introduced bias. A statistically significant difference in mean platelet volume (MPV) was observed between the groups at the screening visit, with the bedinvetmab group showing higher values than the grapiprant group within the reference range. However, the clinical significance of this difference remains unclear. Phosphorus was significantly lower after treatment compared to baseline in grapiprant group, which was consistent with the previously published study 30 . Although the change over time in the bedinvetmab group did not reach statistical significance (p-value approaching significance), a similar downward trend was observed. As none of the dogs developed clinical signs associated with hypophosphatemia during the study, the clinical relevance of this finding is unknown. However, nonsteroidal anti-inflammatory drug (NSAID)-induced hypophosphatemia has been reported in humans and rats. 31 – 33 . The incidence of AEs was similar between the bedinvetmab and grapiprant groups. In the bedinvetmab group, the most common VeDDRA SOC category of AEs involved “skin and appendages” (4/16 dogs: 25%), with a rate consistent with findings from the field study performed in the US, which reported 26.7% 4 . In contrast, the most common VeDDRA SOC category of AEs in the grapiprant group were “digestive tract disorders” (3/16 dogs: 18.8%), and it is well recognized that NSAIDs can be associated with such AEs. While none of the gastrointestinal AEs were classified as severe, one case led to the withdrawal of the subject from the study. The incidence of gastrointestinal AEs in this study aligned with a previous study, which reported 17.0% 24 . The limitation of the study is that due to nature of the non-inferiority study design, dog owners were aware that their dogs were receiving active treatment, either bedinvetmab or grapiprant, which may have introduced bias into the subjective outcomes. Additionally, the sample size was relatively small. However, the primary objective was to demonstrate that bedinvetmab is non-inferior to grapiprant in improving limb use and the sample size was selected based on appropriate sample size estimations for the primary outcome measure. The study was not powered or specifically designed to detect statistically significant differences between the two treatment groups. Consequently, the drop-out of even 1–2 dogs out of 16 dogs in each group (6.3%-12.5% of the group) could have had a disproportionate effect on day 56 measurements. It is important to note that the bedinvetmab group had significantly worse baseline scores in SNoRE 3.0 and CBPI QOL compared to the grapiprant group, which may have allowed for a greater degree of improvement. This non-inferiority study demonstrated that bedinvetmab is non-inferior to grapiprant based on objective gait analysis. Additionally, both subjective and objective data support the efficacy of bedinvetmab for the control of pain associated with OA. Data from the current study supports both bedinvetmab and grapiprant are appropriate first-line treatments for dogs with OA pain. Materials and methods Study design This was a prospective, single center, randomized, double-blind, noninferiority study comparing the efficacy of bedinvetmab with a nonsteroidal anti-inflammatory drug (grapiprant) using force plate gait analysis (FPGA). The study was conducted over a 2-month period with outcome measures gathered at screening (approximately 1–2 weeks before day 0) and day 0 (prior to treatment), and every 2 weeks (Table 1 ). The primary endpoint timepoint of this study determined a priori was Day 42, thus any dogs who dropped out of the study before Day 42 were replaced. NC State University Institutional Animal Care and Use Committee (IACUC) approved this study and all procedures (IACUC#23–193), and the study was approved by the Hospital Clinical Studies Review Board. All dog owners signed a written consent form following a detailed verbal explanation of the study protocol. All methods were performed in accordance with relevant guidelines and regulations. All animal work was conducted according to the guidelines outlined in the Animal Welfare Act of 1966 and the Health Research Extension Act of 1985. This study was carried out and reported in compliance with the ARRIVE and PetSORT guidelines. Table 1 Timeline of data collection Screening Day0 (Baseline) Day 14 Day 28 Day 42 Day 56 Radiography ✓ Canine OsteoArthritis Staging Tool ✓ Clinical pathology ✓ ✓ ✓ Bedinvetmab/placebo injection ✓ ✓ Static body weight distribution ✓ ✓ ✓ Patient Global Impression of Change ✓ ✓ ✓ ✓ Force plate gait analysis ✓ ✓ ✓ ✓ ✓ ✓ Veterinary assessments ✓ ✓ ✓ ✓ ✓ ✓ Client-reported outcome measures ✓ ✓ ✓ ✓ ✓ ✓ Recruitment Dogs were recruited from the community surrounding the North Carolina State University (NCSU) via recruitment marketing through the Clinical Studies Core https://cvm.ncsu.edu/research/research-labs/clinical-studies/ (estimated human population locally of 1 million) from September 2023 to October 2024 (the last clinical appointment was Dec 2024). Recruitment also included advertisements via NCSU websites, e-mails to local practices and NC State employees, local radio advertisements and via CVM social media (X and Facebook). Owners were contacted by telephone and an initial screening was conducted. If initial inclusion criteria were met, the primary care veterinarian was contacted and asked for permission from the study personnel to screen the dog. Case selection Client-owned dogs ≥ 1year-old and > 20kg with clinical and radiographic evidence of OA in at least one appendicular joint exclusively at hips and/or stifles were recruited 16 , 17 , 34 . The minimum weight stipulation was to help to ensure the dogs would not be too small for GRF data collection using the force plate. Dogs were permitted to have orthopedic problems in the other joints, but the most affected site needed to be stifle and/or hip, and to have a predominantly single limb lameness associated with the most affected joint. Dogs were required to have clinical signs of OA-associated joint pain confirmed by gait evaluation, veterinary assessment, Liverpool OsteoArthritis in Dogs (LOAD), and radiography (appendicular joints, spine), otherwise be in general good health or have stable chronic conditions, and able to complete the study in the opinion of the veterinarian. Health status was assessed by physical examination, medical history, and clinical pathology evaluations (complete blood count, serum biochemistry profile, and urinalysis including sediment examination). The recruited dogs were also required to have a LOAD score of ≥ 10 on screening and Day 0 30 . Among the client-reported outcome measures (CROMs), LOAD was used to define the inclusion criteria. This is because most enrolled patients were expected to present with noticeable single-limb lameness, with one limb more affected than the other, and the LOAD was originally developed for similar patient populations. Dogs that had clinically relevant abnormal clinical pathology findings, spinal orthopedic abnormalities, or neurologic abnormalities that affected gait were excluded. Other exclusion criteria were concomitant disorders that may have affected evaluations for the study, and other joint diseases (such as immune-mediated joint disease). Dogs that had major surgery within 6 months of screening were excluded, as were dogs that had surgeries that could confound the evaluation of OA pain (acute inflammatory pain due to surgery). The required wash-out period was at least 2 weeks for NSAIDs or short-acting steroids, 4 weeks for long-acting steroids, and 8 weeks for bedinvetmab before day 0. Dogs were required to be either not receiving nutritional supplements and/or other analgesics (e.g., amantadine, gabapentin, tramadol), or have been on them for 6 weeks or more before the start of the study. If dogs were receiving those treatments, their dosage and frequency were not changed during the study. Randomization and blinding Computer-generated randomization tables were created by NCSU-College of Veterinary Medicine (CVM) pharmacy prior to the start of the study. Dogs were randomized based on the order of enrollment at the site. The randomization table was maintained in confidence by the pharmacy. All test articles were also kept securely in NCSU-CVM pharmacy. Both the owners and study personnel were blinded throughout the study period. Unblinding occurred only after the completion of all the study activities (data collection and case selection). Treatment Eligible dogs were randomized (1:1) to monthly subcutaneous (SC) administration of bedinvetmab (0.5-1.0 mg/kg) plus daily oral placebo or daily oral grapiprant (2 mg/kg) plus monthly SC administration of saline (same volume as bedinvetmab: 1ml) beginning on Day 0. Owners were instructed to give the oral medication 30 minutes to 1 hour before a meal and at approximately the same time each day. Compliance with dosing was evaluated by reconciling the returned pills with what was dispensed, with counting performed by personnel not involved in the study. Examination Physical, orthopedic, and neurologic examinations were performed, and data were captured using an electronic data capture system (RedCap). During the orthopedic examination, every joint of each limb was examined by a veterinarian experienced in evaluating pain associated with OA in dogs (ME), and joints were graded for pain, as described previously 35 . Assessments for crepitus, effusion, thickening, and range of motion were recorded, but not used in analysis. The manus and pes were considered as one joint region for evaluation purposes. Other appendicular joints evaluated were carpus, elbow, shoulder, tarsus, stifle, and hip. Spinal column segments were examined and graded for pain. The axial skeleton was evaluated by dividing the spine into cervical, thoracic (T1-10), thoraco-lumbar (T11-L2), lumbar (L3-6), and lumbosacral regions. Scores for pain at each joint or spinal segment ranged from 0 to 4 (0: no pain, 4: severe pain). Scores were recorded on the Joint Evaluation Scoring SystEm canine (JESSEcanine) 35 . Radiography Radiographs were taken under sedation with a mu-opiate combined with alpha-2 adrenergic agonist, for example, butorphanol 0.3 mg/kg/IV and dexmedetomidine 0.003–0.005 mg/kg/IV. However, the choice of drug and dose was adapted according to the dog’s health condition. Orthogonal views of all appendicular joints (mani, carpi, elbows, shoulders, pes, tarsi, stifles and hips) and lateral views of the spine (cervical, thoracic (T1-9), thoracolumbar (T10-L6), and lumbosacral) were made, as described in the published paper 2 . To minimize ionizing radiation exposure, where appropriate, radiographs were centered on the midpoint of the limb or spinal segment to reduce the number of individual exposures used. A subjective overall severity score was assigned to each joint based on a numerical rating scale where 0 = no radiographic abnormalities identified and 10 = most severe radiographic OA, as described previously (range 0-200) 36 . Radiographs were assessed using a DICOM viewer (Horos ver. 3.3.6) by a veterinarian experienced in evaluating canine OA (ME). Outcome measures Client-reported outcome measures CROMs were used as previously described. The Liverpool OsteoArthritis in Dogs (LOAD) and Canine Brief Pain Inventory (CBPI) have been shown to be valid measures of the impact of OA- pain in dogs 11 , 19 , 21 . Sleep and Nighttime Restlessness Evaluation Score Questionnaire version 2.0 and 3.0 (SNoRE) were used to collect data regarding sleep quality 20 , 37 . Client specific outcome measure (CSOM) was also used to evaluate the impact of OA- pain 38 . The CROMs were completed by the same dog owner throughout the study period. For the LOAD and CSOM, the sum of each item score was calculated. For all the CROMs except for CBPI QOL, a decrease in score following Day 0, indicates improvement. Treatment success of LOAD was considered if there was a decrease from baseline of ≥ 4 in LOAD (Minimal Clinically Important Difference, MCID) 22 . For CBPI [pain severity scores (PSS) and pain interference scores (PIS)] and the SNoRE, the average of each item was calculated. Treatment success of CBPI was considered if there was a decrease from baseline of ≥ 1 in PSS and ≥ 2 in PIS 21 . Canine OsteoArthritis Staging Tool At screening, the Canine OsteoArthritis Staging Tool (COAST) was used for staging the impact of OA on patients (0 = clinically normal, 4 = severe OA) 39 . Based on the published papers, the items considered as the risk factors for OA in this study were orthopedic disease without radiographic evidence of OA (e.g. hip subluxation), traumatic joint injury/surgery, certain breed, overweight (BCS ≥ 7; scale, 1–9) 40 – 43 . Patient Global Impression of Change Patient Global Impression of Change (PGIC) is a single question that asks owners to assess how their dog’s condition has changed since the start of treatment, and was adopted from the previously published work in humans 44 . It uses a 7-point scale to rate overall improvement. Owners are asked to choose the description that best reflects their dog's condition, including: “very much improved (score of 1)”, “much improved (2)”, “minimally improved (3)”, “no change (4)”, “minimally worse (5)”, “much worse (6)”, or “very much worse (7)”. Force plate gait analysis Ground reaction forces (GRFs) were collected using dual in series FPs (AMTI, Watertown, MA, USA) and custom software (Sharon software, Dewitt, MI, USA). Velocity and acceleration were measured by means of five photoelectric cells placed 0.5 m apart and coupled with a triggered timer system 30 . The dogs were trotted across the force plates at a velocity of 1.9–2.2 m/s and acceleration of each dog was restricted to ± 0.5 m/s 34 . A trial from which data were retained for analysis consisted of a full forefoot strike on each plate without another foot being on the plate at the same time, followed by an ipsilateral hindfoot strike in the same fashion on each plate. Thus, data from all four limbs were obtained in a single pass. A single trained observer evaluated each foot strike and subsequent force profile and determined whether or not the trial should be retained. A single handler gaited all the dogs for each trial and timepoint. Five valid trials were collected for each dog at each timepoint. Peak vertical force (PVF) and vertical impulse (VI) were the GRFs extracted, and the means of the five trials at each visit were used for analysis. The determination of appropriate trials and final selection of trials was made by one investigator (ME) prior to knowing which treatment dogs had been receiving (prior to unblinding). All forces were normalized to body weight and expressed as a percentage of bodyweight. An index limb (where there is the most severely affected joint) was identified based on clinical signs of joint pain, muscle atrophy and limb use. The change from baseline in PVF and VI of the index limb was calculated for analysis. Treatment success of PVF and VI were considered if increase from baseline of ≥ 3.5% in each parameter 14 , 34 . Static body weight distribution while standing Static body weight distribution data were recorded using a pressure-sensitive walkway (PSW; 7100 QL Virtual Sensor 4, Tekscan™, Boston, MA). They were collected with the dog in the standing position as described elsewhere 45 . Before each use, the PSW was calibrated. Ten sets of data were collected for each dog at each time point and the first five trials where visual inspection of the data indicated steady state of bodyweight distribution on each limb for at least 5 seconds (regardless of where bodyweight was distributed to) were used for analysis. For each data set used in the analysis, the mean percentage bodyweight distribution for the 5-s steady-state period was used. Safety outcome measures and analysis The owners were asked to report any unusual events during the study period. An adverse event (AE) was defined as any observation, undesirable experience, or reaction in the dogs that was unfavorable and unintended and occurred after the initiation of treatment, whether or not considered to be related to the treatment. Blood work and urinalysis were repeated on day 28 and 56. Statistical analysis The primary analysis was a noninferiority analysis of bedinvetmab versus grapiprant, conducted using a per-protocol approach. The endpoint for this analysis was PVF success on day 42. A 90% confidence interval for the difference between the proportion of animals with PVF success in each group was determined using Monte Carlo bootstrapping with replacement (n = 10,000 resamples from the data). Additionally, Clopper-Pearson exact confidence intervals were calculated for the proportion of animals with success based on definitions for both PVF and LOAD on days 14, 28, 42, and 56. In addition to the non-inferiority analysis, the two groups were compared for differences in age, body weight, radiographic score and BCS at screening, using independent t-tests for variables that appeared approximately normally distributed and the Mann-Whitney U test where they did not. A Fisher exact test was used to compare the COAST stages between groups. Further, CROMs and other outcomes were compared over time between the two groups using mixed effects models, which incorporate a random intercept for individual animals in order to adjust for the lack of independence introduced by repeated measures over time. Numeric variables (LOAD, PVF, VI, CBPI-PSS and PIS, Static body weight distribution, SNoRE 2.0 and 3.0, CSOM, lameness index, joint pain scores) were analyzed using linear mixed effects models (applying log transformations where necessary to meet model assumptions), while ordinal variables (CBPI QOL, PGIC, joint pain index, were compared using ordinal logistic mixed effects models; success rates, where defined, were analyzed using binary logistic mixed effects models. All models included effects of group, time (treated categorically), and an interaction of group and time. The analyses above were performed using IBM SPSS Statistics v. 30 (IBM, Endicott, NY) as well as R v. 4.4.3 (packages included ExactCIdiff, lme4 and ordinal). Where referred to, statistical significance indicates p < 0.05. For blood work, adjusted p-values for multiple comparisons were calculated using the Tukey-Kramer method in JMP Pro 16 (JMP Statistical Discovery LLC, Cary, NC) to compare each time point. After adjustment, the critical p-value threshold was 0.0024 for CBC values and 0.0021 for chemistry values. Sample size estimation The sample size calculation was based on assumptions derived from published data by our group using force plate gait analysis. Treatment success was defined as a 3.5% increase from baseline in peak vertical force (PVF) 14 , 34 . Using this, the success rate for the placebo group was assumed to be 7.5% 16,17 , while the success rate for grapiprant was assumed to be 50% 30 , resulting in a treatment difference of 42.5% (50% − 7.5%). The non-inferiority margin was set at half of this difference as recommended by the FDA ( https://www.fda.gov/media/78504/download ), yielding 21.25% (42.5% / 2). The bedinvetmab success rate was assumed at 74.4% based our recent work using classic NSAIDs 16 , 17 . To achieve 80% power at α = 0.05 and demonstrate that the two-sided 90% confidence interval (CI) for the treatment difference between bedinvetmab and grapiprant exceeds the non-inferiority margin, 14 animals per treatment group were required. Assuming a drop-out rate of 20%, a minimum of 16 patients per group were to be included. Declarations Conflict of interest The funder was not involved in the study design, collection, analysis, interpretation of data, or the decision to submit it for publication. However, the manuscript went through an internal review and approval process at Zoetis Inc before submission to check for potential disclosure of confidential information. Funding Statement The authors declare that this study received funding from Zoetis Inc. (NC State Grant # 2023–2676). Data availability statement The raw data supporting the conclusions of this article will be made available by the corresponding author, without undue reservation. Ethics statement The animal studies were approved by North Carolina State University Institutional Animal Care and Use Committee (IACUC # 23–193). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent was obtained from the owners for the participation of their animals in this study. Author Contribution ME, JFI, and BDXL: study design. ME, LB, CTF, and RT: patient recruitment, data collection/analysis, entry, and verification (QC). ME and KL: statistical analysis. ME, KL, JFI, and BDXL: original draft manuscript preparation. All authors contributed to the article and approved the submitted version. RT is currently at the Department of Veterinary Clinical Sciences, College of Veterinary Medicine at Washinton State University. Acknowledgement We acknowledge Dr. Elizabeth Kawecki-Wright, Tracey Cole, Savannah Aker, Ashley Maney, Margaret Edel, for helping with recruitment and data collection. Data Availability The raw data supporting the conclusions of this article will be made available by the corresponding author, without undue reservation. References Wright, A. et al. Identification of canine osteoarthritis using an owner-reported questionnaire and treatment monitoring using functional mobility tests. J Small Anim Pract 63 , 609-618 (2022). https://doi.org:10.1111/jsap.13500 Enomoto, M. et al. Prevalence of radiographic appendicular osteoarthritis and associated clinical signs in young dogs. Sci Rep 14 , 2827 (2024). https://doi.org:10.1038/s41598-024-52324-9 Corral, M. J. et al. A prospective, randomized, blinded, placebo-controlled multisite clinical study of bedinvetmab, a canine monoclonal antibody targeting nerve growth factor, in dogs with osteoarthritis. Vet Anaesth Analg 48 , 943-955 (2021). https://doi.org:10.1016/j.vaa.2021.08.001 Michels, G. M., Honsberger, N. A., Walters, R. R., Kira, S. T. J. & Cleaver, D. M. A prospective, randomized, double-blind, placebo-controlled multisite, parallel-group field study in dogs with osteoarthritis conducted in the United States of America evaluating bedinvetmab, a canine anti-nerve growth factor monoclonal antibody. Vet Anaesth Analg 50 , 446-458 (2023). https://doi.org:10.1016/j.vaa.2023.06.003 Innes, J. F., Fuller, C. J., Grover, E. R., Kelly, A. L. & Burn, J. F. Randomised, double-blind, placebo-controlled parallel group study of P54FP for the treatment of dogs with osteoarthritis. Vet Rec 152 , 457-460 (2003). https://doi.org:10.1136/vr.152.15.457 Reid, J., Gildea, E., Davies, V., Thompson, J. & Scott, M. Measuring the effect of the anti-nerve growth factor antibodies bedinvetmab and frunevetmab on quality of life in dogs and cats with osteoarthritis using a validated health-related quality of life outcome measure: an observational real-world study. Front Vet Sci 11 , 1395360 (2024). https://doi.org:10.3389/fvets.2024.1395360 Gruen, M. E. et al. 2022 AAHA Pain Management Guidelines for Dogs and Cats. J Am Anim Hosp Assoc 58 , 55-76 (2022). https://doi.org:10.5326/JAAHA-MS-7292 Cachon, T. et al. COAST Development Group's international consensus guidelines for the treatment of canine osteoarthritis. Front Vet Sci 10 , 1137888 (2023). https://doi.org:10.3389/fvets.2023.1137888 Monteiro, B. P. et al. 2022 WSAVA guidelines for the recognition, assessment and treatment of pain. J Small Anim Pract 64 , 177-254 (2023). https://doi.org:10.1111/jsap.13566 Brown, D. C., Boston, R. C. & Farrar, J. T. Comparison of force plate gait analysis and owner assessment of pain using the Canine Brief Pain Inventory in dogs with osteoarthritis. J Vet Intern Med 27 , 22-30 (2013). https://doi.org:10.1111/jvim.12004 Walton, M. B., Cowderoy, E. C., Wustefeld-Janssens, B., Lascelles, B. D. X. & Innes, J. F. Mavacoxib and meloxicam for canine osteoarthritis: a randomised clinical comparator trial. Vet Rec 175 (2014). https://doi.org:10.1136/vr.102435 Budsberg, S. C., Verstraete, M. C. & Soutas-Little, R. W. Force plate analysis of the walking gait in healthy dogs. Am J Vet Res 48 , 915-918 (1987). Voss, K., Galeandro, L., Wiestner, T., Haessig, M. & Montavon, P. M. Relationships of body weight, body size, subject velocity, and vertical ground reaction forces in trotting dogs. Vet surg 39 , 863-869 (2010). https://doi.org:10.1111/j.1532-950X.2010.00729.x Conzemius, M. G. et al. Best practices for measuring and reporting ground reaction forces in dogs. Vet surg 51 , 385-396 (2022). https://doi.org:10.1111/vsu.13772 Voss, K., Imhof, J., Kaestner, S. & Montavon, P. M. Force plate gait analysis at the walk and trot in dogs with low-grade hindlimb lameness. Vet Comp Orthopaed 20 , 299-304 (2007). https://doi.org:10.1160/Vcot-07-01-0008 Kampa, N. et al. Study of the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the treatment of dogs with hip osteoarthritis: A prospective, block-randomized, double-blinded, placebo-controlled clinical trial. Front Vet Sci 10 , 1033188 (2023). https://doi.org:10.3389/fvets.2023.1033188 Kampa, N. et al. Evaluation of the comparative efficacy of green lipped mussel plus krill oil extracts (EAB-277), Biota orientalis extracts or NSAIDs for the treatment of dogs with osteoarthritis associated pain: a blinded, placebo-controlled study. Front Vet Sci 11 , 1464549 (2024). https://doi.org:10.3389/fvets.2024.1464549 Brown, D. C., Boston, R. C., Coyne, J. C. & Farrar, J. T. Development and psychometric testing of an instrument designed to measure chronic pain in dogs with osteoarthritis. Am J Vet Res 68 , 631-637 (2007). https://doi.org:10.2460/ajvr.68.6.631 Brown, D. C., Boston, R. C., Coyne, J. C. & Farrar, J. T. Ability of the canine brief pain inventory to detect response to treatment in dogs with osteoarthritis. J Am Vet Med Assoc 233 , 1278-1283 (2008). https://doi.org:10.2460/javma.233.8.1278 Knazovicky, D., Tomas, A., Motsinger-Reif, A. & Lascelles, B. D. Initial evaluation of nighttime restlessness in a naturally occurring canine model of osteoarthritis pain. PeerJ 3 , e772 (2015). https://doi.org:10.7717/peerj.772 Brown, D. C., Bell, M. & Rhodes, L. Power of treatment success definitions when the Canine Brief Pain Inventory is used to evaluate carprofen treatment for the control of pain and inflammation in dogs with osteoarthritis. Am J Vet Res 74 , 1467-1473 (2013). Innes, J. F., Morton, M. A. & Lascelles, B. D. X. Minimal clinically-important differences for the 'Liverpool Osteoarthritis in Dogs' (LOAD) and the 'Canine Orthopedic Index' (COI) client-reported outcomes measures. PloS one 18 , e0280912 (2023). https://doi.org:10.1371/journal.pone.0280912 Lascelles, B. D. et al. A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain. BMC Vet Res 11 , 101 (2015). https://doi.org:10.1186/s12917-015-0413-x Rausch-Derra, L., Huebner, M., Wofford, J. & Rhodes, L. A Prospective, Randomized, Masked, Placebo-Controlled Multisite Clinical Study of Grapiprant, an EP4 Prostaglandin Receptor Antagonist (PRA), in Dogs with Osteoarthritis. J Vet Intern Med 30 , 756-763 (2016). https://doi.org:10.1111/jvim.13948 Walton, M. B., Cowderoy, E. C., Wustefeld-Janssens, B., Lascelles, B. D. & Innes, J. F. Mavacoxib and meloxicam for canine osteoarthritis: a randomised clinical comparator trial. Vet Rec 175 , 280 (2014). https://doi.org:10.1136/vr.102435 Dworkin, R. H. et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain 9 , 105-121 (2008). https://doi.org:10.1016/j.jpain.2007.09.005 Innes, J. F., Morton, M. A. & Lascelles, B. D. X. Minimal clinically-important differences for the 'Liverpool Osteoarthritis in Dogs' (LOAD) and the 'Canine Orthopedic Index' (COI) client-reported outcomes measures. PloS one 18 (2023). https://doi.org:ARTN e0280912 10.1371/journal.pone.0280912 Ogura, K. et al. Minimal clinically important differences in SF-36 global score: Current value in orthopedic oncology. J Orthop Res 39 , 2116-2123 (2021). https://doi.org:10.1002/jor.24944 Scott, W. & McCracken, L. M. Patients' impression of change following treatment for chronic pain: global, specific, a single dimension, or many? J Pain 16 , 518-526 (2015). https://doi.org:10.1016/j.jpain.2015.02.007 Enomoto, M. et al. Response to treatment with grapiprant as part of a standard multimodal regimen in young dogs with appendicular joint osteoarthritis associated pain. Front Vet Sci 11 (2024). https://doi.org:ARTN 1461628 10.3389/fvets.2024.1461628 Weighty issue of osteoarthritis , (2019). Gomaa, A. A., Hassan, H. A. & Ghaneimah, S. A. Effect of Aspirin and Indomethacin on the Serum and Urinary Calcium, Magnesium and Phosphate. Pharmacol Res 22 , 59-70 (1990). https://doi.org:Doi 10.1016/1043-6618(90)90744-X Skeid, M. S., Pedersen-Bjergaard, U., Kristensen, P. L. & Brandi, L. NSAID-induced symptomatic hypophosphataemia. Brit J Clin Pharmaco 82 , 1399-1401 (2016). https://doi.org:10.1111/bcp.13061 Gagnon, A. et al. Therapeutic response analysis in dogs with naturally occurring osteoarthritis. Vet Anaesth Analg 44 , 1373-1381 (2017). https://doi.org:10.1016/j.vaa.2017.07.008 Rowlison de Ortiz, A. et al. Initial exploration of the discriminatory ability of the PetPace collar to detect differences in activity and physiological variables between healthy and osteoarthritic dogs. Front Pain Res (Lausanne) 3 , 949877 (2022). https://doi.org:10.3389/fpain.2022.949877 Enomoto, M., Baines, E. A., Roe, S. C., Marcellin-Little, D. J. & Lascelles, B. D. X. Defining the rate of, and factors influencing, radiographic progression of osteoarthritis of the canine hip joint. Vet Rec 189 , e516 (2021). https://doi.org:10.1002/vetr.516 Mondino, A. et al. Development and validation of a sleep questionnaire, SNoRE 3.0, to evaluate sleep in companion dogs. Sci Rep 13 , 13340 (2023). https://doi.org:10.1038/s41598-023-40048-1 Lascelles, B. D. X. et al. A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain. BMC Vet Res 11 (2015). https://doi.org:ARTN 101 10.1186/s12917-015-0413-x Cachon, T. et al. Face validity of a proposed tool for staging canine osteoarthritis: Canine OsteoArthritis Staging Tool (COAST). Vet J 235 , 1-8 (2018). https://doi.org:10.1016/j.tvjl.2018.02.017 Anderson, K. L. et al. Prevalence, duration and risk factors for appendicular osteoarthritis in a UK dog population under primary veterinary care. Sci Rep 8 , 5641 (2018). https://doi.org:10.1038/s41598-018-23940-z Anderson, K. L., Zulch, H., O'Neill, D. G., Meeson, R. L. & Collins, L. M. Risk Factors for Canine Osteoarthritis and Its Predisposing Arthropathies: A Systematic Review. Front Vet Sci 7 , 220 (2020). https://doi.org:10.3389/fvets.2020.00220 Smith, G. K. et al. Chronology of hip dysplasia development in a cohort of 48 Labrador retrievers followed for life. Vet Surg 41 , 20-33 (2012). https://doi.org:10.1111/j.1532-950X.2011.00935.x van Hagen, M. A., Ducro, B. J., van den Broek, J. & Knol, B. W. Incidence, risk factors, and heritability estimates of hind limb lameness caused by hip dysplasia in a birth cohort of boxers. Am J Vet Res 66 , 307-312 (2005). https://doi.org:10.2460/ajvr.2005.66.307 Farrar, J. T., Troxel, A. B., Stott, C., Duncombe, P. & Jensen, M. P. Validity, reliability, and clinical importance of change in a 0-10 numeric rating scale measure of spasticity: a post hoc analysis of a randomized, double-blind, placebo-controlled trial. Clin Ther 30 , 974-985 (2008). https://doi.org:10.1016/j.clinthera.2008.05.011 Lascelles, B. D. X. et al. Evaluation of Functional Outcome After BFX (R) Total Hip Replacement Using a Pressure Sensitive Walkway. Vet Surg 39 , 71-77 (2010). https://doi.org:10.1111/j.1532-950X.2009.00607.x Additional Declarations No competing interests reported. Supplementary Files 20250729supplementralfiles.docx Cite Share Download PDF Status: Published Journal Publication published 10 Feb, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 21 Oct, 2025 Reviews received at journal 16 Oct, 2025 Reviewers agreed at journal 01 Oct, 2025 Reviews received at journal 30 Sep, 2025 Reviewers agreed at journal 29 Sep, 2025 Reviewers agreed at journal 29 Sep, 2025 Reviews received at journal 28 Sep, 2025 Reviewers agreed at journal 10 Sep, 2025 Reviewers agreed at journal 09 Sep, 2025 Reviewers invited by journal 09 Sep, 2025 Editor assigned by journal 03 Sep, 2025 Editor invited by journal 14 Aug, 2025 Submission checks completed at journal 08 Aug, 2025 First submitted to journal 08 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7303674","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":515315545,"identity":"fc29b624-2011-44c5-9477-1a03a55c0586","order_by":0,"name":"Masataka Enomoto","email":"","orcid":"","institution":"North Carolina State University","correspondingAuthor":false,"prefix":"","firstName":"Masataka","middleName":"","lastName":"Enomoto","suffix":""},{"id":515315546,"identity":"5fcaeae3-5bdc-4e01-a4bc-6331ee0f8e99","order_by":1,"name":"Lauren Buslinger","email":"","orcid":"","institution":"North Carolina State University","correspondingAuthor":false,"prefix":"","firstName":"Lauren","middleName":"","lastName":"Buslinger","suffix":""},{"id":515315547,"identity":"b857d6cc-c7fa-4ad3-9fe0-ae637fe6f375","order_by":2,"name":"Connor Thonen-Fleck","email":"","orcid":"","institution":"North Carolina State University","correspondingAuthor":false,"prefix":"","firstName":"Connor","middleName":"","lastName":"Thonen-Fleck","suffix":""},{"id":515315548,"identity":"dcc87591-62e8-4c7e-b183-0ac9fc6391b3","order_by":3,"name":"Rubia Tomacheuski","email":"","orcid":"","institution":"North Carolina State University","correspondingAuthor":false,"prefix":"","firstName":"Rubia","middleName":"","lastName":"Tomacheuski","suffix":""},{"id":515315549,"identity":"06b688df-01a9-4fb7-9ee1-b4de2588d12b","order_by":4,"name":"Kim Love","email":"","orcid":"","institution":"K. R. Love Quantitative Consulting and Collaboration","correspondingAuthor":false,"prefix":"","firstName":"Kim","middleName":"","lastName":"Love","suffix":""},{"id":515315550,"identity":"500ddf0a-ca1e-4872-b52d-8f5bd62f0d88","order_by":5,"name":"John F. Innes","email":"","orcid":"","institution":"Movement Referrals Veterinary Specialists","correspondingAuthor":false,"prefix":"","firstName":"John","middleName":"F.","lastName":"Innes","suffix":""},{"id":515315551,"identity":"860713b8-d926-4afc-97aa-267b97cc9503","order_by":6,"name":"B. Duncan. X Lascelles","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYDCCA8wNIEqGH8pnbCCsBaKGR7KBZC0GB4jVwncjsfHjjxobHuPbzY8/8zDYyG44QECL5JmDzdI8x9J4zO4cM5PmYUgzJqjF4HhjgzRjw2Eesxs5bMw8DIcTCWs5zNj882fDfx7jGTnMQIf9J0LL8cY2Cd6GAzwGEjkMQIcdIKwF6Jc2a55jyTwSN9LMJOcYJBvPJKSF70by4Zs/auzk+GckP/7wpsJOto+QFnR3kqZ8FIyCUTAKRgEOAADGCUPB9f14wgAAAABJRU5ErkJggg==","orcid":"","institution":"North Carolina State University","correspondingAuthor":true,"prefix":"","firstName":"B.","middleName":"Duncan. X","lastName":"Lascelles","suffix":""}],"badges":[],"createdAt":"2025-08-05 19:38:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7303674/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7303674/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-026-37626-4","type":"published","date":"2026-02-10T15:59:15+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":91504697,"identity":"0e4c18bf-2c8f-48b3-8228-3b2e7fc4c990","added_by":"auto","created_at":"2025-09-17 08:09:30","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":82091,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT flow diagram describing all cases recruited for the study. n: number.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7303674/v1/5884732055f9511ed57bd422.jpg"},{"id":91504698,"identity":"77541797-0437-46a9-9310-846dfcef3e30","added_by":"auto","created_at":"2025-09-17 08:09:30","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":48600,"visible":true,"origin":"","legend":"\u003cp\u003ePercent change (Mean ± SD) from baseline in the peak vertical force. Orange line indicates bedinvetmab group and blue line indicated grapiprant group. Please note that the number of dogs per each group at each timepoint was 16, except on day 14 and day 56 for grapiprant (n=15 and n=14, respectively), and on day 56 for bedinvetmab (n=15).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7303674/v1/24cc5090cc75032ca57caad7.jpg"},{"id":91505443,"identity":"9ac2d1ce-72dd-4fcd-bb1a-c73e95267e98","added_by":"auto","created_at":"2025-09-17 08:17:30","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":47330,"visible":true,"origin":"","legend":"\u003cp\u003ePercent change (Mean ± SD) from baseline in the vertical impulse. Orange line indicates bedinvetmab group and blue line indicated grapiprant group. Please note that the number of dogs per each group at each timepoint was 16, except on day 14 and day 56 for grapiprant (n=15 and n=14, respectively), and on day 56 for bedinvetmab (n=15).\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7303674/v1/b2b60d2c96184a9e39f5d489.jpg"},{"id":91505441,"identity":"84a2202e-8e63-4204-b30c-44303506e859","added_by":"auto","created_at":"2025-09-17 08:17:30","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":45904,"visible":true,"origin":"","legend":"\u003cp\u003eMean (± SD) change from day 0 in total Liverpool Osteoarthritis in Dogs (LOAD) score.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7303674/v1/3e36d58084c08cda97da5085.jpg"},{"id":102785373,"identity":"ddba3f2e-3467-445c-ab8b-627b5201029d","added_by":"auto","created_at":"2026-02-16 16:05:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1579655,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7303674/v1/f6d77a50-ac62-4564-bf1c-1968fca8ac60.pdf"},{"id":91504700,"identity":"7b2015f9-eaec-4841-b485-410407e50c3f","added_by":"auto","created_at":"2025-09-17 08:09:30","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":32420,"visible":true,"origin":"","legend":"","description":"","filename":"20250729supplementralfiles.docx","url":"https://assets-eu.researchsquare.com/files/rs-7303674/v1/9a24e9e9ac544f1f7c449d64.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"A noninferiority trial evaluating the efficacy of bedinvetmab compared to grapiprant for osteoarthritis-pain in dogs using force plate gait analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOsteoarthritis (OA) is a degenerative joint disease, often resulting in chronic pain and disability. It is a highly prevalent condition, with an estimated 20\u0026ndash;37% of dogs over the age of 1 year affected\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Additionally, a recent study found that approximately 40% of young dogs, aged 8 months to 4 years, showed radiographic signs of osteoarthritis (rOA) in one or more appendicular joints. Among these, 40\u0026ndash;60% of dogs with rOA had clinical signs in the affected joints, depending on the criteria used to define joint pain\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe primary goal of OA pain management is to alleviate discomfort and improve quality of life (QoL). Non-steroidal anti-inflammatory drugs (NSAIDs) were the standard and only pharmacological therapy with robust evidence of efficacy until recently. However, the recent approval of a novel class of analgesic, bedinvetmab (Librela\u0026trade;), has provided an alternative first line treatment option\u003csup\u003e\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Bedinvetmab, a fully canine monoclonal antibody, targets nerve growth factor (NGF), which is a key mediator of OA pain signaling in dogs. It has been licensed in over 50 countries, including the United States, Canada, Europe, the United Kingdom, Latin America, Asia, and Australia. Current pain management guidelines, including those from AAHA, WSAVA, and COAST, recommend both NSAIDs and anti-NGF monoclonal antibodies as appropriate first-line treatments for dogs with OA pain\u003csup\u003e\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. However, while clinical studies have demonstrated bedinvetmab's efficacy using subjective outcome measures\u003csup\u003e\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e, its effectiveness has not yet been evaluated with objective measures such as force plate gait analysis (FPGA). FPGA measures limb use by measuring ground reaction forces (GRFs), and limb use is decreased in the presence of joint pain. FPGA has been used in studies for evaluation of the efficacy of analgesics for OA-related joint pain in dogs\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Accordingly, this study was designed to assess the efficacy of bedinvetmab in comparison to that of grapiprant for the management of pain in dogs with naturally occurring OA as measured using objective gait analysis over a 2-month period. The authors hypothesized that bedinvetmab would be non-inferior to grapiprant based on improvement in objectively measured GRFs.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAs a result of advertising, 211 inquiries were received, and 89 dogs were screened (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Thirty-seven dogs received study drug, however, 3 dogs dropped out of the study prior to day 42; [due to diarrhea associated with dietary change (n\u0026thinsp;=\u0026thinsp;1), unable to collect FPGA due to overlapping strikes (n\u0026thinsp;=\u0026thinsp;1), and acute forelimb lameness due to recurrent tendinitis (n\u0026thinsp;=\u0026thinsp;1)], and these dogs were replaced; none of these events were considered to be related to study drug. Additionally, 2 dogs were excluded from analysis due to significant protocol deviation (1 dog in bedinvetmab group did not receive oral medication (placebo) for 2 weeks, 1 dog in grapiprant group was unable to perform force plate gait analysis within the targeted velocity on day 42). Collectively, a total of 32 dogs remained for analysis: 13 different pure breeds in total across 19 dogs; the remaining 13 dogs were mixed breeds. The most common pure breeds were Golden Retriever (n\u0026thinsp;=\u0026thinsp;5), and Labrador Retriever (n\u0026thinsp;=\u0026thinsp;3). (Table\u0026nbsp;\u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Three dogs dropped out of the study after day 42, 1 dog in the bedinvetmab group (cruciate ligament rupture) and 2 dogs in grapiprant group (cruciate ligament rupture or gastrointestinal issues). Data were not collected from one dog in the grapiprant group at day 14 due to an owner health issue. At screening, body weight was significantly lower in the grapiprant group compared to the bedinvetmab group (p\u0026thinsp;=\u0026thinsp;0.04). However, there were no significant differences in age, body condition score (BCS), radiographic score, and Canine OsteoArthritis Staging Tool (COAST) between groups. Overall compliance for daily medication was excellent, and 96.4% of placebo/grapiprant prescribed was utilized.\u003c/p\u003e\u003cp\u003eTable 2 Demographics of enrolled dogs at screening visit. (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and range)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDemographic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroups\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGrapiprant (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7 (1.3\u0026ndash;13.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 (3.5\u0026ndash;12.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0 (1.3\u0026ndash;13.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody weight (kg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1 (21.3\u0026ndash;52.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.3 (20.2\u0026ndash;46.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e33.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7 (20.2\u0026ndash;52.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody condition score (scale, 1\u0026ndash;9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 (4\u0026ndash;7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9 (4\u0026ndash;7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 (4\u0026ndash;7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex Male\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1M, 12 CM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 M, 6CM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2M, 18CM\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3SF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1F, 8SF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1F, 11SF\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal radiographic score (0-200)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9 (4\u0026ndash;44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4 (3\u0026ndash;35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8 (3\u0026ndash;44)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOAST (0\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 (3\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 (3\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 (3\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eM: intact male, F: intact female, CM: castrated male, SF: spayed female, COAST: Canine OsteoArthritis Staging Tool\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eForce plate gait analysis\u003c/h2\u003e\u003cdiv id=\"Sec4\" class=\"Section3\"\u003e\u003ch2\u003eDay 42 (primary endpoint timepoint)\u003c/h2\u003e\u003cp\u003eOn day 42, the peak vertical force (PVF) treatment success rate was 68.8% [95% confidence interval (CI)\u0026thinsp;=\u0026thinsp;41.3\u0026ndash;89.0] for bedinvetmab and 56.3% (95%CI\u0026thinsp;=\u0026thinsp;29.9\u0026ndash;80.2) for grapiprant (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The difference in success rate between the two groups (grapiprant - bedinvetmab) was \u0026minus;\u0026thinsp;12.5% with the two-sided 90%CI for the difference between the two proportions of -37.5\u0026ndash;18.8%. Given that the upper bound of this interval (18.8%) is less than the pre-specified non-inferiority margin of 21.25%, bedinvetmab was concluded to be non-inferior to grapiprant. Furthermore, the p-value for evaluating whether the difference in success rates between the two groups was less than the pre-specified margin of 21.25% was \u0026lt;\u0026thinsp;0.05, meeting the conventional threshold for statistical significance and further supporting the conclusion of non-inferiority. The day 42 mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD percent increase in PVF and vertical impulse (VI), respectively, compared to day 0 was 7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8% and 4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5% for the bedinvetmab group and 6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7% and 6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1% for the grapiprant group (both variables significant for both groups, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).). (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\n\u003ch3\u003eChanges over time\u003c/h3\u003e\n\u003cp\u003eOverall, a significant improvement was seen in PVF and VI in both bedinvetmab and grapiprant groups compared to baseline (day 0 prior to treatment) (Tables\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e5\u003c/span\u003e and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e6\u003c/span\u003e, and Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean percent change from baseline in PVF was 7.6% (3.8% bodyweight) for the bedinvetmab group and 6.9% (3.9% bodyweight) for the grapiprant group throughout the study (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e). At all-time points, the mean change in PVF exceeded the suggested threshold (3.5% change from baseline) for clinical significance. The mean percent change from baseline in VI was 5.8% for the bedinvetmab group and 5.7% for the grapiprant group. The mean change in VI also surpassed the threshold at all time points, except on day 14 in the grapiprant group.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSuccess rate and 95% confidence interval (CI) for treatment success, defined as an increase of \u0026ge;\u0026thinsp;3.5% from baseline in peak vertical force (PVF). n: number of dogs\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTimepoint\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAnimals (n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSuccesses (n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSuccess (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCI for success\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e68.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e41.3%, 89.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e66.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e38.4%, 88.2%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e75.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e47.6%, 92.7%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e56.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e29.9%, 80.2%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e68.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e41.3%, 89.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e56.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e29.9%, 80.2%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e66.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e38.4%, 88.2%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e78.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e49.2%, 95.3%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverall\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e69.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e66.2%, 73.3%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e64.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e54.1%, 74.9%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMean change (\u0026plusmn;\u0026thinsp;SD (range)) from baseline in PVF and VI expressed as a percentage of baseline value. n: number of dogs. PVF: peak vertical force, VI: vertical impulse\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eTimepoint\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range): %\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range): %\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e8.14\u0026thinsp;\u0026plusmn;\u0026thinsp;8.49 (-2.26, 27.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e5.03\u0026thinsp;\u0026plusmn;\u0026thinsp;6.60 (-6.51, 16.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e7.10\u0026thinsp;\u0026plusmn;\u0026thinsp;10.70 (-7.55, 24.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e3.51\u0026thinsp;\u0026plusmn;\u0026thinsp;10.05 (-14.15, 33.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e7.03\u0026thinsp;\u0026plusmn;\u0026thinsp;6.55 (-3.12, 20.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e6.50\u0026thinsp;\u0026plusmn;\u0026thinsp;6.46 (-1.78, 19.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e5.24\u0026thinsp;\u0026plusmn;\u0026thinsp;8.07 (-4.37, 20.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e4.21\u0026thinsp;\u0026plusmn;\u0026thinsp;9.86 (-8.50, 25.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e7.54\u0026thinsp;\u0026plusmn;\u0026thinsp;7.03 (-4.22, 17.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e6.03\u0026thinsp;\u0026plusmn;\u0026thinsp;8.77 (-4.94, 24.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e4.28\u0026thinsp;\u0026plusmn;\u0026thinsp;10.31 (-7.03, 27.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e6.51\u0026thinsp;\u0026plusmn;\u0026thinsp;11.33 (-11.44, 34.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e7.87\u0026thinsp;\u0026plusmn;\u0026thinsp;8.84 (-5.46, 24.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e10.19\u0026thinsp;\u0026plusmn;\u0026thinsp;9.83 (-3.26, 30.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e6.65\u0026thinsp;\u0026plusmn;\u0026thinsp;11.45 (-11.85, 27.81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e8.59\u0026thinsp;\u0026plusmn;\u0026thinsp;11.44 (-3.61, 39.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverall\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e7.64\u0026thinsp;\u0026plusmn;\u0026thinsp;7.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e6.86\u0026thinsp;\u0026plusmn;\u0026thinsp;7.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e5.80\u0026thinsp;\u0026plusmn;\u0026thinsp;9.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e5.65\u0026thinsp;\u0026plusmn;\u0026thinsp;10.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMean (\u0026plusmn;\u0026thinsp;SD (range) PVF) and VI expressed as a percentage of bodyweight (BW). n: number of dogs, PVF: peak vertical force, VI: vertical impulse\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eTimepoint\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range): %BW\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range): %BW\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eScreening\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e60.44\u0026thinsp;\u0026plusmn;\u0026thinsp;12.56 (26.28, 77.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e60.50\u0026thinsp;\u0026plusmn;\u0026thinsp;11.40 (38.27, 77.43)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e8.29\u0026thinsp;\u0026plusmn;\u0026thinsp;1.44 (4.27, 10.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e7.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73 (4.71, 10.46)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eDay 0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e60.25\u0026thinsp;\u0026plusmn;\u0026thinsp;12.20 (24.57, 77.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e61.40\u0026thinsp;\u0026plusmn;\u0026thinsp;11.29 (39.48, 79.91)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e8.31\u0026thinsp;\u0026plusmn;\u0026thinsp;1.55 (3.94, 10.84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e8.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.61 (5.52, 10.44)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e64.43\u0026thinsp;\u0026plusmn;\u0026thinsp;11.08 (31.20, 80.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e63.88\u0026thinsp;\u0026plusmn;\u0026thinsp;9.53 (42.52, 77.44)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e8.81\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41 (4.91, 10.97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e8.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.28 (5.68, 10.08)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e83.96\u0026thinsp;\u0026plusmn;\u0026thinsp;11.48 (29.68, 75.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e65.16\u0026thinsp;\u0026plusmn;\u0026thinsp;11.30 (41.00, 83.97)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e8.69\u0026thinsp;\u0026plusmn;\u0026thinsp;1.43 (4.53, 10.81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e8.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.45 (5.40, 10.41)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e64.41\u0026thinsp;\u0026plusmn;\u0026thinsp;11.75 (27.05, 76.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e64.45\u0026thinsp;\u0026plusmn;\u0026thinsp;8.92 (43.50, 78.44)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e8.62\u0026thinsp;\u0026plusmn;\u0026thinsp;1.49 (4.00, 10.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e8.50\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57 (5.42, 12.01)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e67.13\u0026thinsp;\u0026plusmn;\u0026thinsp;6.72 (54.10, 80.68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e67.21\u0026thinsp;\u0026plusmn;\u0026thinsp;9.25 (49.87, 79.21)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e9.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97 (6.77, 10.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e8.53\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39 (5.74, 10.85)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMean change (\u0026plusmn;\u0026thinsp;SD (range)) from baseline in PVF and VI expressed as a percentage of bodyweight (BW). n: number of dogs. PVF: peak vertical force, VI: vertical impulse\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eTimepoint\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range): %BW\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range): %BW\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e4.17\u0026thinsp;\u0026plusmn;\u0026thinsp;3.56 (-1.57, 9.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e2.55\u0026thinsp;\u0026plusmn;\u0026thinsp;4.17 (-5.20, 9.03)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e0.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81 (-0.70, 2.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e0.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72 (-1.4, 1.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e3.71\u0026thinsp;\u0026plusmn;\u0026thinsp;3.30 (-2.42, 9.56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e3.76\u0026thinsp;\u0026plusmn;\u0026thinsp;4.05 (-1.22-13.24)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e0.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 (-0.4, 1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6 (-0.65, 1.47)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e4.16\u0026thinsp;\u0026plusmn;\u0026thinsp;4.08 (-2.83, 11.36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e3.05\u0026thinsp;\u0026plusmn;\u0026thinsp;4.85 (-3.95, 13.78)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e0.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88 (-0.80, 2.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91 (-1.12, 2.30)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e4.50\u0026thinsp;\u0026plusmn;\u0026thinsp;5.70 (-4.23, 16.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e5.50\u0026thinsp;\u0026plusmn;\u0026thinsp;4.78 (-2.24, 16.98)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e0.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93 (-1.1, 2.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e0.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69 (-0.35, 2.29)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eClient-reported outcome measures (CROMs)\u003c/p\u003e\u003cp\u003eAt baseline, there was a significant difference in the Canine Brief Pain Inventory (CBPI) QOL and Sleep and Nighttime Restlessness Evaluation Score Questionnaire (SNoRE) version 3.0 between groups, with the bedinvetmab group having worse scores than the grapiprant group (Supplemental files 1 and 2). Overall, pain and associated clinical signs were significantly improved in both groups after treatment for all CROMs (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Although no significant differences in any CROMs were observed between the groups after treatment, generally numerically greater improvement was seen in the bedinvetmab group than the grapiprant group (Tables\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e7\u003c/span\u003e and \u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e8\u003c/span\u003e, and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eUsing minimally clinically important difference (MCID) values [reduction of \u0026ge;\u0026thinsp;4 from baseline in Liverpool Osteoarthritis in Dogs (LOAD)], the treatment success for the bedinvetmab group was 75% and for the grapiprant group was 56.3% at day 42. Seven dogs enrolled in the study had CBPI pain severity score (PSS)\u0026thinsp;\u0026lt;\u0026thinsp;2 and/or pain interference score (PIS)\u0026thinsp;\u0026lt;\u0026thinsp;2 at day 0 (3 dogs in bedinvetmab and 4 dogs in grapiprant groups). When only dogs that had CBPI PSS\u0026thinsp;\u0026ge;\u0026thinsp;2 and PIS\u0026thinsp;\u0026ge;\u0026thinsp;2 at day 0 were included, our results showed a success rate of 61.5% for bedinvetmab and 46.2% for grapiprant at day 42 (Supplemental file 3).\u003c/p\u003e\u003cp\u003eBoth groups showed continued improvement over time based on Patient Global Impression of Change (PGIC, supplemental file 4). Overall, a higher proportion of dogs were rated as 'very much improved' or 'much improved' in the bedinvetmab group (62.0%) compared to the grapiprant group (41.0%). Although this difference was not statistically significant, the bedinvetmab group showed a greater overall improvement than the grapiprant group.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMean LOAD\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range) and mean change from baseline in LOAD\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range) at each timepoint. n: number of dogs, LOAD: Liverpool Osteoarthritis in Dogs.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime point\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMean change from baseline\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eScreen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e21.81\u0026thinsp;\u0026plusmn;\u0026thinsp;6.42 (10, 31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e22.00\u0026thinsp;\u0026plusmn;\u0026thinsp;5.34 (12, 33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e23.69\u0026thinsp;\u0026plusmn;\u0026thinsp;6.44 (13, 35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e21.25\u0026thinsp;\u0026plusmn;\u0026thinsp;6.60 (11, 39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e17.75\u0026thinsp;\u0026plusmn;\u0026thinsp;5.15 (8, 27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-5.94\u0026thinsp;\u0026plusmn;\u0026thinsp;5.07 (-17, 3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e17.07\u0026thinsp;\u0026plusmn;\u0026thinsp;5.73 (6, 27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-3.00\u0026thinsp;\u0026plusmn;\u0026thinsp;5.67 (-14, 4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e14.88\u0026thinsp;\u0026plusmn;\u0026thinsp;4.27 (9, 23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-8.81\u0026thinsp;\u0026plusmn;\u0026thinsp;5.96 (-23, 0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e16.38\u0026thinsp;\u0026plusmn;\u0026thinsp;6.49 (1, 28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-4.88\u0026thinsp;\u0026plusmn;\u0026thinsp;6.15 (-19, 3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e14.38\u0026thinsp;\u0026plusmn;\u0026thinsp;6.71 (6, 33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-9.31\u0026thinsp;\u0026plusmn;\u0026thinsp;7.40 (-25, 3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e16.19\u0026thinsp;\u0026plusmn;\u0026thinsp;6.92 (1, 30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-5.06\u0026thinsp;\u0026plusmn;\u0026thinsp;6.18 (-19, 3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e12.47\u0026thinsp;\u0026plusmn;\u0026thinsp;6.00 (5, 28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-10.47\u0026thinsp;\u0026plusmn;\u0026thinsp;6.97 (-25, -1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e15.50\u0026thinsp;\u0026plusmn;\u0026thinsp;7.73 (1, 31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e-6.14\u0026thinsp;\u0026plusmn;\u0026thinsp;7.15 (-19, 7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSuccess rate and 95% confidence interval (CI) for treatment success, defined as an increase of \u0026ge;\u0026thinsp;4 from day 0 in LOAD. n: number of dogs, Liverpool Osteoarthritis in Dogs.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime point\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAnimals (n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSuccesses (n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSuccess (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCI for success\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e75.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e47.6%, 92.7%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e33.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e11.8%, 61.6%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e81.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e54.4%, 96.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e62.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e35.4%, 84.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e75.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e47.6%, 92.7%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e56.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e29.9%, 80.2%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e86.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e59.5%, 98.3%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e64.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e35.1%, 87.2%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverall\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e79.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e74.1%, 85.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrapiprant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e54.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e40.1%, 68.1%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eOther assessments\u003c/p\u003e\u003cp\u003eThe veterinarian-assessed index joint pain score significantly decreased irrespective of group over time (P\u0026thinsp;=\u0026thinsp;0.039). Static body weight distribution data also showed a significant improvement in both groups at day 56 compared to baseline and day 28. (Supplemental file 5)\u003c/p\u003e\u003cp\u003eSafety assessments\u003c/p\u003e\u003cp\u003eBlood work and urinalysis were performed at screening and every month after treatment. Overall, there were no clinically meaningful differences between the groups at the start of the study, and no clinically meaningful changes over time within or between the groups. A statistically significant difference in mean platelet volume (MPV) was observed between the groups at the screening visit, with the bedinvetmab group showing higher values than the grapiprant group. However, mean MPV values in both groups remained within the reference range. Three dogs in the bedinvetmab group and one dog in the grapiprant group had MPV values exceeding the reference range at screening. Phosphorus was significantly lower after treatment compared to baseline in the grapiprant group, although the mean values at those time points stayed within the reference range (supplemental file 6).\u003c/p\u003e\u003cp\u003eAdverse events (AEs) were in line with respective label expectations. Although some occurred at higher frequency in one group or the other, the incidence of AEs was similar between the bedinvetmab and grapiprant groups. One or more adverse events occurred in 7/16 dogs in the bedinvetmab group and 8/16 dogs in the grapiprant group (Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e9\u003c/span\u003e). The most common category of AEs involved skin and appendages in the bedinvetmab group and digestive tract disorders in the grapiprant group. Three musculoskeletal AEs were observed; one dog in each treatment group developed a cruciate ligament rupture contralateral to the index limb diagnosed on day 56; in addition, one dog in the bedinvetmab group had mild transient unilateral forelimb lameness before the day 14 visit that resolved without treatment. For both groups, most AEs were mild and unlikely to be related to investigational drug. In addition to management of the cruciate ligament ruptures, two dogs in the bedinvetmab group received a short course of antibiotics for dermatitis (which resolved by the following visit), one dog in the grapiprant group was treated with antibiotics for a subclinical lower urinary tract infection (resolved within a week) and one dog in the grapiprant group received probiotics for diarrhea (which resolved within several days).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 9\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAll adverse events (AEs) following treatment with bedinvetmab or grapiprant. Data are presented as n (%); n: number of dogs (all animals enrolled). Please note that some dogs had multiple adverse events.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSystemic organ class clinical signs (VeDDRA)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBedinvetmab (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGrapiprant (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal number of AEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin and appendage disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRenal and urinary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDigestive tract disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEar and labyrinth disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMusculoskeletal disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBehavioral disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEye disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOral cavity disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated bedinvetmab was non-inferior to grapiprant based on treatment success for an increase in peak vertical force (PVF) in the index limb during force plate gait analysis (FPGA) on day 42, thus meeting the primary efficacy endpoint. Both groups showed significant improvement from the baseline in objective and subjective outcome measures. Although not statistically significant, numerically greater improvement was observed in the bedinvetmab group compared to the grapiprant group in client-reported outcome measures (CROMs). These findings support the efficacy of bedinvetmab for managing osteoarthritis-associated pain in dogs.\u003c/p\u003e\u003cp\u003eAt screening, there was a statistically significant difference between the two groups with respect to body weight. Body weight is a well-known factor influencing force plate data, and previous studies demonstrated that PVF and vertical impulse (VI) have strong positive correlations with body weight\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. In this study, ground reaction forces were normalized to body weight to minimize its impact and ensure accurate interpretation, as suggested\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eGait analysis has been validated as an objective measure of changes in limb use as it relates to joint pain in dogs.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e In particular, the PVF and the VI are commonly used to determine efficacy of therapeutics in OA studies of dogs.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e A recent review paper suggested that a change from baseline in both PVF and VI over a short time period (less than 6 months) of 3.5% of baseline values (equivalent to 2% bodyweight change from baseline in the index hindlimb) is the minimum value that should be considered clinically important.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e In the current study, the mean percent change from baseline in PVF and VI exceeded the suggested threshold for clinical significance at all time points, except for VI on day 14 in the grapiprant group. In previously published studies, the actual change from baseline in PVF was measured after six weeks of NSAIDs treatment in dogs with hip OA\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. The findings in the current study were comparable to these previous studies \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Overall, the GRF data from the current study indicates that both bedinvetmab and grapiprant are effective treatment options for OA in dogs.\u003c/p\u003e\u003cp\u003eStatic weight bearing distribution has also been used to evaluate therapeutic efficacy. A significant improvement was observed in both groups on day 56 compared to baseline and day 28. Unlike dynamic assessments such as force plate gait analysis, no immediate improvement was noted. This may be due to the time required to normalize posture following long-term postural adaptations.\u003c/p\u003e\u003cp\u003eCBPI, LOAD, Client Specific Outcome Measure (CSOM), and SNoRE have been validated as subjective measures to assess pain and/or clinical signs associated with OA in dogs.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e To evaluate the efficacy of new analgesics, two analytical methods have been commonly used; reduction of pain/disability scores from baseline and binary outcome (success/failure).\u003csup\u003e11,19,21,22\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eOverall, pain and associated clinical signs were significantly improved after treatment based on CROMs. Although the study did not include a placebo control group, the degree of improvement observed was comparable to results reported in previous studies \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. In a prior comparator study evaluating mavacoxib versus meloxicam, the mean reduction in LOAD scores from baseline at week 6 (day 42) ranged from 3.8 to 4.3. Similarly, the mean decreases in CBPI PSS and PIS at week 6 ranged from 0.85 to 1.38 and 1.44 to 1.45, respectively. Grapiprant produced similar improvements in our study as shown in Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e7\u003c/span\u003e and supplemental file 2, while bedinvetmab showed greater improvement with a mean reduction in LOAD of 9.31, a decrease in CBPI PSS of 2.06, and a reduction in CBPI PIS of 2.53.\u003c/p\u003e\u003cp\u003eBinary outcome (e.g. success/failure designation) thresholds have been suggested for CBPI and LOAD changes over time.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e For CBPI, treatment success and failure have been defined, and the success was considered as a reduction of \u0026ge;\u0026thinsp;1 in PSS and \u0026ge;\u0026thinsp;2 in PIS.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e More recently, a reduction of \u0026ge;\u0026thinsp;4 in LOAD was suggested as minimal clinically important differences.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e When analyzing only the subset of dogs with baseline CBPI PSS\u0026thinsp;\u0026ge;\u0026thinsp;2 and PIS\u0026thinsp;\u0026ge;\u0026thinsp;2, our results showed a success rate of 61.5% for bedinvetmab and 38.4% for grapiprant at Day 28. These outcomes are in line with previously published placebo-controlled studies where Day 28 CBPI success rates were 43.5% and 47.4% for bedinvetmab\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,4\u003c/sup\u003e and 48.1% for grapiprant.\u003c/p\u003e\u003cp\u003eOn day 14, dogs treated with bedinvetmab showed a mean reduction in LOAD scores of 5.94, surpassing the MCID of 4. In contrast, the grapiprant group had a mean reduction of 3.00, which did not reach the MCID. Both groups continued to show further improvement over the course of the study, with total mean reductions of 8.6 points for bedinvetmab and 4.8 points for grapiprant. The mean success rate for bedinvetmab group was 79.5% and for grapiprant group was 54.1%.\u003c/p\u003e\u003cp\u003eThe PGIC is an anchor-based questionnaire primarily used to assess global changes based on the owner's perception of how much their dog has improved compared to before treatment\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. The CROMs quantify changes in specific symptoms or indicators (e.g., pain intensity, functional ability) while the PGIC provides global perspective on overall improvement. Importantly, a statistically significant reduction in a dog\u0026rsquo;s pain score compared to placebo may not translate into observable improvements in behavior or activity at home. If the PGIC does not indicate a clear and meaningful improvement, statistical significance of other outcome measures may be questioned\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Therefore, the PGIC serves as a crucial complement to CROMs, helping to ensure that treatment effects are both statistically valid and clinically meaningful\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Both treatment groups demonstrated progressive improvement over the duration of the trial, as measured by the PGIC. However, overall, a higher proportion of dogs were rated as 'very much improved' or 'much improved' in the bedinvetmab group (62.0%) compared to the grapiprant group (41.0%).\u003c/p\u003e\u003cp\u003eThe joint pain score of the index joint significantly decreased over 2 months of the study period following the treatment. Our assumption is that this was due to treatment, however, it is important to remember that none of the joint pain scoring systems, including ours, have been sufficiently validated. Additionally, the examiner was aware that all dogs received active treatment, which may have introduced bias.\u003c/p\u003e\u003cp\u003eA statistically significant difference in mean platelet volume (MPV) was observed between the groups at the screening visit, with the bedinvetmab group showing higher values than the grapiprant group within the reference range. However, the clinical significance of this difference remains unclear. Phosphorus was significantly lower after treatment compared to baseline in grapiprant group, which was consistent with the previously published study\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Although the change over time in the bedinvetmab group did not reach statistical significance (p-value approaching significance), a similar downward trend was observed. As none of the dogs developed clinical signs associated with hypophosphatemia during the study, the clinical relevance of this finding is unknown. However, nonsteroidal anti-inflammatory drug (NSAID)-induced hypophosphatemia has been reported in humans and rats. \u003csup\u003e\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe incidence of AEs was similar between the bedinvetmab and grapiprant groups. In the bedinvetmab group, the most common VeDDRA SOC category of AEs involved \u0026ldquo;skin and appendages\u0026rdquo; (4/16 dogs: 25%), with a rate consistent with findings from the field study performed in the US, which reported 26.7%\u003csup\u003e4\u003c/sup\u003e. In contrast, the most common VeDDRA SOC category of AEs in the grapiprant group were \u0026ldquo;digestive tract disorders\u0026rdquo; (3/16 dogs: 18.8%), and it is well recognized that NSAIDs can be associated with such AEs. While none of the gastrointestinal AEs were classified as severe, one case led to the withdrawal of the subject from the study. The incidence of gastrointestinal AEs in this study aligned with a previous study, which reported 17.0%\u003csup\u003e24\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe limitation of the study is that due to nature of the non-inferiority study design, dog owners were aware that their dogs were receiving active treatment, either bedinvetmab or grapiprant, which may have introduced bias into the subjective outcomes. Additionally, the sample size was relatively small. However, the primary objective was to demonstrate that bedinvetmab is non-inferior to grapiprant in improving limb use and the sample size was selected based on appropriate sample size estimations for the primary outcome measure. The study was not powered or specifically designed to detect statistically significant differences between the two treatment groups. Consequently, the drop-out of even 1\u0026ndash;2 dogs out of 16 dogs in each group (6.3%-12.5% of the group) could have had a disproportionate effect on day 56 measurements. It is important to note that the bedinvetmab group had significantly worse baseline scores in SNoRE 3.0 and CBPI QOL compared to the grapiprant group, which may have allowed for a greater degree of improvement.\u003c/p\u003e\u003cp\u003eThis non-inferiority study demonstrated that bedinvetmab is non-inferior to grapiprant based on objective gait analysis. Additionally, both subjective and objective data support the efficacy of bedinvetmab for the control of pain associated with OA. Data from the current study supports both bedinvetmab and grapiprant are appropriate first-line treatments for dogs with OA pain.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eStudy design\u003c/p\u003e\u003cp\u003eThis was a prospective, single center, randomized, double-blind, noninferiority study comparing the efficacy of bedinvetmab with a nonsteroidal anti-inflammatory drug (grapiprant) using force plate gait analysis (FPGA). The study was conducted over a 2-month period with outcome measures gathered at screening (approximately 1\u0026ndash;2 weeks before day 0) and day 0 (prior to treatment), and every 2 weeks (Table\u0026nbsp;\u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The primary endpoint timepoint of this study determined \u003cem\u003ea priori\u003c/em\u003e was Day 42, thus any dogs who dropped out of the study before Day 42 were replaced. NC State University Institutional Animal Care and Use Committee (IACUC) approved this study and all procedures (IACUC#23\u0026ndash;193), and the study was approved by the Hospital Clinical Studies Review Board. All dog owners signed a written consent form following a detailed verbal explanation of the study protocol. All methods were performed in accordance with relevant guidelines and regulations. All animal work was conducted according to the guidelines outlined in the Animal Welfare Act of 1966 and the Health Research Extension Act of 1985. This study was carried out and reported in compliance with the ARRIVE and PetSORT guidelines.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab9\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eTimeline of data collection\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eScreening\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDay0 (Baseline)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDay 14\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDay 28\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDay 42\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eDay 56\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRadiography\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCanine OsteoArthritis Staging Tool\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClinical pathology\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBedinvetmab/placebo injection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStatic body weight distribution\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatient Global Impression of Change\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eForce plate gait analysis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVeterinary assessments\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClient-reported outcome measures\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e✓\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eRecruitment\u003c/p\u003e\u003cp\u003eDogs were recruited from the community surrounding the North Carolina State University (NCSU) via recruitment marketing through the Clinical Studies Core \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://cvm.ncsu.edu/research/research-labs/clinical-studies/\u003c/span\u003e\u003cspan address=\"https://cvm.ncsu.edu/research/research-labs/clinical-studies/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (estimated human population locally of 1\u0026nbsp;million) from September 2023 to October 2024 (the last clinical appointment was Dec 2024). Recruitment also included advertisements via NCSU websites, e-mails to local practices and NC State employees, local radio advertisements and via CVM social media (X and Facebook). Owners were contacted by telephone and an initial screening was conducted. If initial inclusion criteria were met, the primary care veterinarian was contacted and asked for permission from the study personnel to screen the dog.\u003c/p\u003e\u003cp\u003eCase selection\u003c/p\u003e\u003cp\u003eClient-owned dogs\u0026thinsp;\u0026ge;\u0026thinsp;1year-old and \u0026gt;\u0026thinsp;20kg with clinical and radiographic evidence of OA in at least one appendicular joint exclusively at hips and/or stifles were recruited\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. The minimum weight stipulation was to help to ensure the dogs would not be too small for GRF data collection using the force plate. Dogs were permitted to have orthopedic problems in the other joints, but the most affected site needed to be stifle and/or hip, and to have a predominantly single limb lameness associated with the most affected joint. Dogs were required to have clinical signs of OA-associated joint pain confirmed by gait evaluation, veterinary assessment, Liverpool OsteoArthritis in Dogs (LOAD), and radiography (appendicular joints, spine), otherwise be in general good health or have stable chronic conditions, and able to complete the study in the opinion of the veterinarian. Health status was assessed by physical examination, medical history, and clinical pathology evaluations (complete blood count, serum biochemistry profile, and urinalysis including sediment examination). The recruited dogs were also required to have a LOAD score of \u0026ge;\u0026thinsp;10 on screening and Day 0\u003csup\u003e30\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAmong the client-reported outcome measures (CROMs), LOAD was used to define the inclusion criteria. This is because most enrolled patients were expected to present with noticeable single-limb lameness, with one limb more affected than the other, and the LOAD was originally developed for similar patient populations. Dogs that had clinically relevant abnormal clinical pathology findings, spinal orthopedic abnormalities, or neurologic abnormalities that affected gait were excluded. Other exclusion criteria were concomitant disorders that may have affected evaluations for the study, and other joint diseases (such as immune-mediated joint disease). Dogs that had major surgery within 6 months of screening were excluded, as were dogs that had surgeries that could confound the evaluation of OA pain (acute inflammatory pain due to surgery). The required wash-out period was at least 2 weeks for NSAIDs or short-acting steroids, 4 weeks for long-acting steroids, and 8 weeks for bedinvetmab before day 0. Dogs were required to be either not receiving nutritional supplements and/or other analgesics (e.g., amantadine, gabapentin, tramadol), or have been on them for 6 weeks or more before the start of the study. If dogs were receiving those treatments, their dosage and frequency were not changed during the study.\u003c/p\u003e\u003cp\u003eRandomization and blinding\u003c/p\u003e\u003cp\u003eComputer-generated randomization tables were created by NCSU-College of Veterinary Medicine (CVM) pharmacy prior to the start of the study. Dogs were randomized based on the order of enrollment at the site. The randomization table was maintained in confidence by the pharmacy. All test articles were also kept securely in NCSU-CVM pharmacy. Both the owners and study personnel were blinded throughout the study period. Unblinding occurred only after the completion of all the study activities (data collection and case selection).\u003c/p\u003e\u003cp\u003eTreatment\u003c/p\u003e\u003cp\u003eEligible dogs were randomized (1:1) to monthly subcutaneous (SC) administration of bedinvetmab (0.5-1.0 mg/kg) plus daily oral placebo or daily oral grapiprant (2 mg/kg) plus monthly SC administration of saline (same volume as bedinvetmab: 1ml) beginning on Day 0. Owners were instructed to give the oral medication 30 minutes to 1 hour before a meal and at approximately the same time each day. Compliance with dosing was evaluated by reconciling the returned pills with what was dispensed, with counting performed by personnel not involved in the study.\u003c/p\u003e\u003cp\u003eExamination\u003c/p\u003e\u003cp\u003ePhysical, orthopedic, and neurologic examinations were performed, and data were captured using an electronic data capture system (RedCap). During the orthopedic examination, every joint of each limb was examined by a veterinarian experienced in evaluating pain associated with OA in dogs (ME), and joints were graded for pain, as described previously\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. Assessments for crepitus, effusion, thickening, and range of motion were recorded, but not used in analysis. The manus and pes were considered as one joint region for evaluation purposes. Other appendicular joints evaluated were carpus, elbow, shoulder, tarsus, stifle, and hip. Spinal column segments were examined and graded for pain. The axial skeleton was evaluated by dividing the spine into cervical, thoracic (T1-10), thoraco-lumbar (T11-L2), lumbar (L3-6), and lumbosacral regions. Scores for pain at each joint or spinal segment ranged from 0 to 4 (0: no pain, 4: severe pain). Scores were recorded on the Joint Evaluation Scoring SystEm canine (JESSEcanine)\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eRadiography\u003c/p\u003e\u003cp\u003eRadiographs were taken under sedation with a mu-opiate combined with alpha-2 adrenergic agonist, for example, butorphanol 0.3 mg/kg/IV and dexmedetomidine 0.003\u0026ndash;0.005 mg/kg/IV. However, the choice of drug and dose was adapted according to the dog\u0026rsquo;s health condition. Orthogonal views of all appendicular joints (mani, carpi, elbows, shoulders, pes, tarsi, stifles and hips) and lateral views of the spine (cervical, thoracic (T1-9), thoracolumbar (T10-L6), and lumbosacral) were made, as described in the published paper \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. To minimize ionizing radiation exposure, where appropriate, radiographs were centered on the midpoint of the limb or spinal segment to reduce the number of individual exposures used. A subjective overall severity score was assigned to each joint based on a numerical rating scale where 0\u0026thinsp;=\u0026thinsp;no radiographic abnormalities identified and 10\u0026thinsp;=\u0026thinsp;most severe radiographic OA, as described previously (range 0-200)\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. Radiographs were assessed using a DICOM viewer (Horos ver. 3.3.6) by a veterinarian experienced in evaluating canine OA (ME).\u003c/p\u003e\u003cp\u003eOutcome measures\u003c/p\u003e\n\u003ch3\u003eClient-reported outcome measures\u003c/h3\u003e\n\u003cp\u003eCROMs were used as previously described. The Liverpool OsteoArthritis in Dogs (LOAD) and Canine Brief Pain Inventory (CBPI) have been shown to be valid measures of the impact of OA- pain in dogs\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Sleep and Nighttime Restlessness Evaluation Score Questionnaire version 2.0 and 3.0 (SNoRE) were used to collect data regarding sleep quality\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. Client specific outcome measure (CSOM) was also used to evaluate the impact of OA- pain\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. The CROMs were completed by the same dog owner throughout the study period. For the LOAD and CSOM, the sum of each item score was calculated. For all the CROMs except for CBPI QOL, a decrease in score following Day 0, indicates improvement. Treatment success of LOAD was considered if there was a decrease from baseline of \u0026ge;\u0026thinsp;4 in LOAD (Minimal Clinically Important Difference, MCID)\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. For CBPI [pain severity scores (PSS) and pain interference scores (PIS)] and the SNoRE, the average of each item was calculated. Treatment success of CBPI was considered if there was a decrease from baseline of \u0026ge;\u0026thinsp;1 in PSS and \u0026ge;\u0026thinsp;2 in PIS\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003ch3\u003eCanine OsteoArthritis Staging Tool\u003c/h3\u003e\n\u003cp\u003eAt screening, the Canine OsteoArthritis Staging Tool (COAST) was used for staging the impact of OA on patients (0\u0026thinsp;=\u0026thinsp;clinically normal, 4\u0026thinsp;=\u0026thinsp;severe OA)\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e. Based on the published papers, the items considered as the risk factors for OA in this study were orthopedic disease without radiographic evidence of OA (e.g. hip subluxation), traumatic joint injury/surgery, certain breed, overweight (BCS\u0026thinsp;\u0026ge;\u0026thinsp;7; scale, 1\u0026ndash;9) \u003csup\u003e\u003cspan additionalcitationids=\"CR41 CR42\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003ePatient Global Impression of Change\u003c/h2\u003e\u003cp\u003ePatient Global Impression of Change (PGIC) is a single question that asks owners to assess how their dog\u0026rsquo;s condition has changed since the start of treatment, and was adopted from the previously published work in humans\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e. It uses a 7-point scale to rate overall improvement. Owners are asked to choose the description that best reflects their dog's condition, including: \u0026ldquo;very much improved (score of 1)\u0026rdquo;, \u0026ldquo;much improved (2)\u0026rdquo;, \u0026ldquo;minimally improved (3)\u0026rdquo;, \u0026ldquo;no change (4)\u0026rdquo;, \u0026ldquo;minimally worse (5)\u0026rdquo;, \u0026ldquo;much worse (6)\u0026rdquo;, or \u0026ldquo;very much worse (7)\u0026rdquo;.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eForce plate gait analysis\u003c/h2\u003e\u003cp\u003eGround reaction forces (GRFs) were collected using dual in series FPs (AMTI, Watertown, MA, USA) and custom software (Sharon software, Dewitt, MI, USA). Velocity and acceleration were measured by means of five photoelectric cells placed 0.5 m apart and coupled with a triggered timer system\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. The dogs were trotted across the force plates at a velocity of 1.9\u0026ndash;2.2 m/s and acceleration of each dog was restricted to \u0026plusmn;\u0026thinsp;0.5 m/s\u003csup\u003e34\u003c/sup\u003e. A trial from which data were retained for analysis consisted of a full forefoot strike on each plate without another foot being on the plate at the same time, followed by an ipsilateral hindfoot strike in the same fashion on each plate. Thus, data from all four limbs were obtained in a single pass. A single trained observer evaluated each foot strike and subsequent force profile and determined whether or not the trial should be retained. A single handler gaited all the dogs for each trial and timepoint. Five valid trials were collected for each dog at each timepoint. Peak vertical force (PVF) and vertical impulse (VI) were the GRFs extracted, and the means of the five trials at each visit were used for analysis. The determination of appropriate trials and final selection of trials was made by one investigator (ME) prior to knowing which treatment dogs had been receiving (prior to unblinding). All forces were normalized to body weight and expressed as a percentage of bodyweight. An index limb (where there is the most severely affected joint) was identified based on clinical signs of joint pain, muscle atrophy and limb use. The change from baseline in PVF and VI of the index limb was calculated for analysis. Treatment success of PVF and VI were considered if increase from baseline of \u0026ge;\u0026thinsp;3.5% in each parameter\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eStatic body weight distribution while standing\u003c/h2\u003e\u003cp\u003eStatic body weight distribution data were recorded using a pressure-sensitive walkway (PSW; 7100 QL Virtual Sensor 4, Tekscan\u0026trade;, Boston, MA). They were collected with the dog in the standing position as described elsewhere\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e. Before each use, the PSW was calibrated. Ten sets of data were collected for each dog at each time point and the first five trials where visual inspection of the data indicated steady state of bodyweight distribution on each limb for at least 5 seconds (regardless of where bodyweight was distributed to) were used for analysis. For each data set used in the analysis, the mean percentage bodyweight distribution for the 5-s steady-state period was used.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eSafety outcome measures and analysis\u003c/h2\u003e\u003cp\u003eThe owners were asked to report any unusual events during the study period. An adverse event (AE) was defined as any observation, undesirable experience, or reaction in the dogs that was unfavorable and unintended and occurred after the initiation of treatment, whether or not considered to be related to the treatment. Blood work and urinalysis were repeated on day 28 and 56.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe primary analysis was a noninferiority analysis of bedinvetmab versus grapiprant, conducted using a per-protocol approach. The endpoint for this analysis was PVF success on day 42. A 90% confidence interval for the difference between the proportion of animals with PVF success in each group was determined using Monte Carlo bootstrapping with replacement (n\u0026thinsp;=\u0026thinsp;10,000 resamples from the data). Additionally, Clopper-Pearson exact confidence intervals were calculated for the proportion of animals with success based on definitions for both PVF and LOAD on days 14, 28, 42, and 56.\u003c/p\u003e\u003cp\u003eIn addition to the non-inferiority analysis, the two groups were compared for differences in age, body weight, radiographic score and BCS at screening, using independent t-tests for variables that appeared approximately normally distributed and the Mann-Whitney U test where they did not. A Fisher exact test was used to compare the COAST stages between groups. Further, CROMs and other outcomes were compared over time between the two groups using mixed effects models, which incorporate a random intercept for individual animals in order to adjust for the lack of independence introduced by repeated measures over time. Numeric variables (LOAD, PVF, VI, CBPI-PSS and PIS, Static body weight distribution, SNoRE 2.0 and 3.0, CSOM, lameness index, joint pain scores) were analyzed using linear mixed effects models (applying log transformations where necessary to meet model assumptions), while ordinal variables (CBPI QOL, PGIC, joint pain index, were compared using ordinal logistic mixed effects models; success rates, where defined, were analyzed using binary logistic mixed effects models. All models included effects of group, time (treated categorically), and an interaction of group and time.\u003c/p\u003e\u003cp\u003eThe analyses above were performed using IBM SPSS Statistics v. 30 (IBM, Endicott, NY) as well as R v. 4.4.3 (packages included ExactCIdiff, lme4 and ordinal). Where referred to, statistical significance indicates p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003eFor blood work, adjusted p-values for multiple comparisons were calculated using the Tukey-Kramer method in JMP Pro 16 (JMP Statistical Discovery LLC, Cary, NC) to compare each time point. After adjustment, the critical p-value threshold was 0.0024 for CBC values and 0.0021 for chemistry values.\u003c/p\u003e\u003cp\u003eSample size estimation\u003c/p\u003e\u003cp\u003eThe sample size calculation was based on assumptions derived from published data by our group using force plate gait analysis. Treatment success was defined as a 3.5% increase from baseline in peak vertical force (PVF)\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. Using this, the success rate for the placebo group was assumed to be 7.5%\u003csup\u003e16,17\u003c/sup\u003e, while the success rate for grapiprant was assumed to be 50%\u003csup\u003e30\u003c/sup\u003e, resulting in a treatment difference of 42.5% (50% \u0026minus;\u0026thinsp;7.5%). The non-inferiority margin was set at half of this difference as recommended by the FDA (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.fda.gov/media/78504/download\u003c/span\u003e\u003cspan address=\"https://www.fda.gov/media/78504/download\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), yielding 21.25% (42.5% / 2). The bedinvetmab success rate was assumed at 74.4% based our recent work using classic NSAIDs\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. To achieve 80% power at α\u0026thinsp;=\u0026thinsp;0.05 and demonstrate that the two-sided 90% confidence interval (CI) for the treatment difference between bedinvetmab and grapiprant exceeds the non-inferiority margin, 14 animals per treatment group were required. Assuming a drop-out rate of 20%, a minimum of 16 patients per group were to be included.\u003c/p\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eConflict of interest\u003c/h2\u003e\u003cp\u003eThe funder was not involved in the study design, collection, analysis, interpretation of data, or the decision to submit it for publication. However, the manuscript went through an internal review and approval process at Zoetis Inc before submission to check for potential disclosure of confidential information.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding Statement\u003c/h2\u003e\u003cp\u003eThe authors declare that this study received funding from Zoetis Inc. (NC State Grant # 2023\u0026ndash;2676).\u003c/p\u003e\u003cp\u003eData availability statement\u003c/p\u003e\u003cp\u003eThe raw data supporting the conclusions of this article will be made available by the corresponding author, without undue reservation.\u003c/p\u003e\u003cp\u003eEthics statement\u003c/p\u003e\u003cp\u003eThe animal studies were approved by North Carolina State University Institutional Animal Care and Use Committee (IACUC # 23\u0026ndash;193). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent was obtained from the owners for the participation of their animals in this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eME, JFI, and BDXL: study design. ME, LB, CTF, and RT: patient recruitment, data collection/analysis, entry, and verification (QC). ME and KL: statistical analysis. ME, KL, JFI, and BDXL: original draft manuscript preparation. All authors contributed to the article and approved the submitted version. RT is currently at the Department of Veterinary Clinical Sciences, College of Veterinary Medicine at Washinton State University.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe acknowledge Dr. Elizabeth Kawecki-Wright, Tracey Cole, Savannah Aker, Ashley Maney, Margaret Edel, for helping with recruitment and data collection.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe raw data supporting the conclusions of this article will be made available by the corresponding author, without undue reservation.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWright, A.\u003cem\u003e et al.\u003c/em\u003e Identification of canine osteoarthritis using an owner-reported questionnaire and treatment monitoring using functional mobility tests. \u003cem\u003eJ Small Anim Pract\u003c/em\u003e \u003cstrong\u003e63\u003c/strong\u003e, 609-618 (2022). https://doi.org:10.1111/jsap.13500\u003c/li\u003e\n\u003cli\u003eEnomoto, M.\u003cem\u003e et al.\u003c/em\u003e Prevalence of radiographic appendicular osteoarthritis and associated clinical signs in young dogs. \u003cem\u003eSci Rep\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 2827 (2024). https://doi.org:10.1038/s41598-024-52324-9\u003c/li\u003e\n\u003cli\u003eCorral, M. J.\u003cem\u003e et al.\u003c/em\u003e A prospective, randomized, blinded, placebo-controlled multisite clinical study of bedinvetmab, a canine monoclonal antibody targeting nerve growth factor, in dogs with osteoarthritis. \u003cem\u003eVet Anaesth Analg \u003c/em\u003e\u003cstrong\u003e48\u003c/strong\u003e, 943-955 (2021). https://doi.org:10.1016/j.vaa.2021.08.001\u003c/li\u003e\n\u003cli\u003eMichels, G. M., Honsberger, N. A., Walters, R. R., Kira, S. T. J. \u0026amp; Cleaver, D. M. A prospective, randomized, double-blind, placebo-controlled multisite, parallel-group field study in dogs with osteoarthritis conducted in the United States of America evaluating bedinvetmab, a canine anti-nerve growth factor monoclonal antibody. \u003cem\u003eVet Anaesth Analg\u003c/em\u003e \u003cstrong\u003e50\u003c/strong\u003e, 446-458 (2023). https://doi.org:10.1016/j.vaa.2023.06.003\u003c/li\u003e\n\u003cli\u003eInnes, J. F., Fuller, C. J., Grover, E. R., Kelly, A. L. \u0026amp; Burn, J. F. Randomised, double-blind, placebo-controlled parallel group study of P54FP for the treatment of dogs with osteoarthritis. \u003cem\u003eVet Rec\u003c/em\u003e \u003cstrong\u003e152\u003c/strong\u003e, 457-460 (2003). https://doi.org:10.1136/vr.152.15.457\u003c/li\u003e\n\u003cli\u003eReid, J., Gildea, E., Davies, V., Thompson, J. \u0026amp; Scott, M. Measuring the effect of the anti-nerve growth factor antibodies bedinvetmab and frunevetmab on quality of life in dogs and cats with osteoarthritis using a validated health-related quality of life outcome measure: an observational real-world study. \u003cem\u003eFront Vet Sci\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 1395360 (2024). https://doi.org:10.3389/fvets.2024.1395360\u003c/li\u003e\n\u003cli\u003eGruen, M. E.\u003cem\u003e et al.\u003c/em\u003e 2022 AAHA Pain Management Guidelines for Dogs and Cats. \u003cem\u003eJ Am Anim Hosp Assoc\u003c/em\u003e \u003cstrong\u003e58\u003c/strong\u003e, 55-76 (2022). https://doi.org:10.5326/JAAHA-MS-7292\u003c/li\u003e\n\u003cli\u003eCachon, T.\u003cem\u003e et al.\u003c/em\u003e COAST Development Group\u0026apos;s international consensus guidelines for the treatment of canine osteoarthritis. \u003cem\u003eFront Vet Sci\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 1137888 (2023). https://doi.org:10.3389/fvets.2023.1137888\u003c/li\u003e\n\u003cli\u003eMonteiro, B. P.\u003cem\u003e et al.\u003c/em\u003e 2022 WSAVA guidelines for the recognition, assessment and treatment of pain. \u003cem\u003eJ Small Anim Pract\u003c/em\u003e \u003cstrong\u003e64\u003c/strong\u003e, 177-254 (2023). https://doi.org:10.1111/jsap.13566\u003c/li\u003e\n\u003cli\u003eBrown, D. C., Boston, R. C. \u0026amp; Farrar, J. T. Comparison of force plate gait analysis and owner assessment of pain using the Canine Brief Pain Inventory in dogs with osteoarthritis. \u003cem\u003eJ Vet Intern Med\u003c/em\u003e \u003cstrong\u003e27\u003c/strong\u003e, 22-30 (2013). https://doi.org:10.1111/jvim.12004\u003c/li\u003e\n\u003cli\u003eWalton, M. B., Cowderoy, E. C., Wustefeld-Janssens, B., Lascelles, B. D. X. \u0026amp; Innes, J. F. Mavacoxib and meloxicam for canine osteoarthritis: a randomised clinical comparator trial. \u003cem\u003eVet Rec\u003c/em\u003e \u003cstrong\u003e175\u003c/strong\u003e (2014). https://doi.org:10.1136/vr.102435\u003c/li\u003e\n\u003cli\u003eBudsberg, S. C., Verstraete, M. C. \u0026amp; Soutas-Little, R. W. Force plate analysis of the walking gait in healthy dogs. \u003cem\u003eAm J Vet Res\u003c/em\u003e \u003cstrong\u003e48\u003c/strong\u003e, 915-918 (1987). \u003c/li\u003e\n\u003cli\u003eVoss, K., Galeandro, L., Wiestner, T., Haessig, M. \u0026amp; Montavon, P. M. Relationships of body weight, body size, subject velocity, and vertical ground reaction forces in trotting dogs. \u003cem\u003eVet surg \u003c/em\u003e\u003cstrong\u003e39\u003c/strong\u003e, 863-869 (2010). https://doi.org:10.1111/j.1532-950X.2010.00729.x\u003c/li\u003e\n\u003cli\u003eConzemius, M. G.\u003cem\u003e et al.\u003c/em\u003e Best practices for measuring and reporting ground reaction forces in dogs. \u003cem\u003eVet surg\u003c/em\u003e \u003cstrong\u003e51\u003c/strong\u003e, 385-396 (2022). https://doi.org:10.1111/vsu.13772\u003c/li\u003e\n\u003cli\u003eVoss, K., Imhof, J., Kaestner, S. \u0026amp; Montavon, P. M. Force plate gait analysis at the walk and trot in dogs with low-grade hindlimb lameness. \u003cem\u003eVet Comp Orthopaed\u003c/em\u003e \u003cstrong\u003e20\u003c/strong\u003e, 299-304 (2007). https://doi.org:10.1160/Vcot-07-01-0008\u003c/li\u003e\n\u003cli\u003eKampa, N.\u003cem\u003e et al.\u003c/em\u003e Study of the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the treatment of dogs with hip osteoarthritis: A prospective, block-randomized, double-blinded, placebo-controlled clinical trial. \u003cem\u003eFront Vet Sci\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 1033188 (2023). https://doi.org:10.3389/fvets.2023.1033188\u003c/li\u003e\n\u003cli\u003eKampa, N.\u003cem\u003e et al.\u003c/em\u003e Evaluation of the comparative efficacy of green lipped mussel plus krill oil extracts (EAB-277), Biota orientalis extracts or NSAIDs for the treatment of dogs with osteoarthritis associated pain: a blinded, placebo-controlled study. \u003cem\u003eFront Vet Sci\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 1464549 (2024). https://doi.org:10.3389/fvets.2024.1464549\u003c/li\u003e\n\u003cli\u003eBrown, D. C., Boston, R. C., Coyne, J. C. \u0026amp; Farrar, J. T. Development and psychometric testing of an instrument designed to measure chronic pain in dogs with osteoarthritis. \u003cem\u003eAm J Vet Res\u003c/em\u003e \u003cstrong\u003e68\u003c/strong\u003e, 631-637 (2007). https://doi.org:10.2460/ajvr.68.6.631\u003c/li\u003e\n\u003cli\u003eBrown, D. C., Boston, R. C., Coyne, J. C. \u0026amp; Farrar, J. T. Ability of the canine brief pain inventory to detect response to treatment in dogs with osteoarthritis. \u003cem\u003eJ Am Vet Med Assoc\u003c/em\u003e \u003cstrong\u003e233\u003c/strong\u003e, 1278-1283 (2008). https://doi.org:10.2460/javma.233.8.1278\u003c/li\u003e\n\u003cli\u003eKnazovicky, D., Tomas, A., Motsinger-Reif, A. \u0026amp; Lascelles, B. D. Initial evaluation of nighttime restlessness in a naturally occurring canine model of osteoarthritis pain. \u003cem\u003ePeerJ\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, e772 (2015). https://doi.org:10.7717/peerj.772\u003c/li\u003e\n\u003cli\u003eBrown, D. C., Bell, M. \u0026amp; Rhodes, L. Power of treatment success definitions when the Canine Brief Pain Inventory is used to evaluate carprofen treatment for the control of pain and inflammation in dogs with osteoarthritis. \u003cem\u003eAm J Vet Res\u003c/em\u003e \u003cstrong\u003e74\u003c/strong\u003e, 1467-1473 (2013). \u003c/li\u003e\n\u003cli\u003eInnes, J. F., Morton, M. A. \u0026amp; Lascelles, B. D. X. Minimal clinically-important differences for the \u0026apos;Liverpool Osteoarthritis in Dogs\u0026apos; (LOAD) and the \u0026apos;Canine Orthopedic Index\u0026apos; (COI) client-reported outcomes measures. \u003cem\u003ePloS one\u003c/em\u003e \u003cstrong\u003e18\u003c/strong\u003e, e0280912 (2023). https://doi.org:10.1371/journal.pone.0280912\u003c/li\u003e\n\u003cli\u003eLascelles, B. D.\u003cem\u003e et al.\u003c/em\u003e A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain. \u003cem\u003eBMC Vet Res\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 101 (2015). https://doi.org:10.1186/s12917-015-0413-x\u003c/li\u003e\n\u003cli\u003eRausch-Derra, L., Huebner, M., Wofford, J. \u0026amp; Rhodes, L. A Prospective, Randomized, Masked, Placebo-Controlled Multisite Clinical Study of Grapiprant, an EP4 Prostaglandin Receptor Antagonist (PRA), in Dogs with Osteoarthritis. \u003cem\u003eJ Vet Intern Med \u003c/em\u003e\u003cstrong\u003e30\u003c/strong\u003e, 756-763 (2016). https://doi.org:10.1111/jvim.13948\u003c/li\u003e\n\u003cli\u003eWalton, M. B., Cowderoy, E. C., Wustefeld-Janssens, B., Lascelles, B. D. \u0026amp; Innes, J. F. Mavacoxib and meloxicam for canine osteoarthritis: a randomised clinical comparator trial. \u003cem\u003eVet Rec\u003c/em\u003e \u003cstrong\u003e175\u003c/strong\u003e, 280 (2014). https://doi.org:10.1136/vr.102435\u003c/li\u003e\n\u003cli\u003eDworkin, R. H.\u003cem\u003e et al.\u003c/em\u003e Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. \u003cem\u003eJ Pain\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, 105-121 (2008). https://doi.org:10.1016/j.jpain.2007.09.005\u003c/li\u003e\n\u003cli\u003eInnes, J. F., Morton, M. A. \u0026amp; Lascelles, B. D. X. Minimal clinically-important differences for the \u0026apos;Liverpool Osteoarthritis in Dogs\u0026apos; (LOAD) and the \u0026apos;Canine Orthopedic Index\u0026apos; (COI) client-reported outcomes measures. \u003cem\u003ePloS one\u003c/em\u003e \u003cstrong\u003e18\u003c/strong\u003e (2023). https://doi.org:ARTN e0280912 10.1371/journal.pone.0280912\u003c/li\u003e\n\u003cli\u003eOgura, K.\u003cem\u003e et al.\u003c/em\u003e Minimal clinically important differences in SF-36 global score: Current value in orthopedic oncology. \u003cem\u003eJ Orthop Res\u003c/em\u003e \u003cstrong\u003e39\u003c/strong\u003e, 2116-2123 (2021). https://doi.org:10.1002/jor.24944\u003c/li\u003e\n\u003cli\u003eScott, W. \u0026amp; McCracken, L. M. Patients\u0026apos; impression of change following treatment for chronic pain: global, specific, a single dimension, or many? \u003cem\u003eJ Pain\u003c/em\u003e \u003cstrong\u003e16\u003c/strong\u003e, 518-526 (2015). https://doi.org:10.1016/j.jpain.2015.02.007\u003c/li\u003e\n\u003cli\u003eEnomoto, M.\u003cem\u003e et al.\u003c/em\u003e Response to treatment with grapiprant as part of a standard multimodal regimen in young dogs with appendicular joint osteoarthritis associated pain. \u003cem\u003eFront Vet Sci\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e (2024). https://doi.org:ARTN 1461628 10.3389/fvets.2024.1461628\u003c/li\u003e\n\u003cli\u003e\u003cem\u003eWeighty issue of osteoarthritis\u003c/em\u003e, \u0026lt;https://www.banfield.com/about-banfield/newsroom/press-releases/2019/banfield-pet-hospitals-ninth-annual-state-of-pet\u0026gt; (2019).\u003c/li\u003e\n\u003cli\u003eGomaa, A. A., Hassan, H. A. \u0026amp; Ghaneimah, S. A. Effect of Aspirin and Indomethacin on the Serum and Urinary Calcium, Magnesium and Phosphate. \u003cem\u003ePharmacol Res\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e, 59-70 (1990). https://doi.org:Doi 10.1016/1043-6618(90)90744-X\u003c/li\u003e\n\u003cli\u003eSkeid, M. S., Pedersen-Bjergaard, U., Kristensen, P. L. \u0026amp; Brandi, L. NSAID-induced symptomatic hypophosphataemia. \u003cem\u003eBrit J Clin Pharmaco\u003c/em\u003e \u003cstrong\u003e82\u003c/strong\u003e, 1399-1401 (2016). https://doi.org:10.1111/bcp.13061\u003c/li\u003e\n\u003cli\u003eGagnon, A.\u003cem\u003e et al.\u003c/em\u003e Therapeutic response analysis in dogs with naturally occurring osteoarthritis. \u003cem\u003eVet Anaesth Analg\u003c/em\u003e \u003cstrong\u003e44\u003c/strong\u003e, 1373-1381 (2017). https://doi.org:10.1016/j.vaa.2017.07.008\u003c/li\u003e\n\u003cli\u003eRowlison de Ortiz, A.\u003cem\u003e et al.\u003c/em\u003e Initial exploration of the discriminatory ability of the PetPace collar to detect differences in activity and physiological variables between healthy and osteoarthritic dogs. \u003cem\u003eFront Pain Res (Lausanne)\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, 949877 (2022). https://doi.org:10.3389/fpain.2022.949877\u003c/li\u003e\n\u003cli\u003eEnomoto, M., Baines, E. A., Roe, S. C., Marcellin-Little, D. J. \u0026amp; Lascelles, B. D. X. Defining the rate of, and factors influencing, radiographic progression of osteoarthritis of the canine hip joint. \u003cem\u003eVet Rec\u003c/em\u003e \u003cstrong\u003e189\u003c/strong\u003e, e516 (2021). https://doi.org:10.1002/vetr.516\u003c/li\u003e\n\u003cli\u003eMondino, A.\u003cem\u003e et al.\u003c/em\u003e Development and validation of a sleep questionnaire, SNoRE 3.0, to evaluate sleep in companion dogs. \u003cem\u003eSci Rep\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 13340 (2023). https://doi.org:10.1038/s41598-023-40048-1\u003c/li\u003e\n\u003cli\u003eLascelles, B. D. X.\u003cem\u003e et al.\u003c/em\u003e A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain. \u003cem\u003eBMC Vet Res\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e (2015). https://doi.org:ARTN 101 10.1186/s12917-015-0413-x\u003c/li\u003e\n\u003cli\u003eCachon, T.\u003cem\u003e et al.\u003c/em\u003e Face validity of a proposed tool for staging canine osteoarthritis: Canine OsteoArthritis Staging Tool (COAST). \u003cem\u003eVet J\u003c/em\u003e \u003cstrong\u003e235\u003c/strong\u003e, 1-8 (2018). https://doi.org:10.1016/j.tvjl.2018.02.017\u003c/li\u003e\n\u003cli\u003eAnderson, K. L.\u003cem\u003e et al.\u003c/em\u003e Prevalence, duration and risk factors for appendicular osteoarthritis in a UK dog population under primary veterinary care. \u003cem\u003eSci Rep\u003c/em\u003e \u003cstrong\u003e8\u003c/strong\u003e, 5641 (2018). https://doi.org:10.1038/s41598-018-23940-z\u003c/li\u003e\n\u003cli\u003eAnderson, K. L., Zulch, H., O\u0026apos;Neill, D. G., Meeson, R. L. \u0026amp; Collins, L. M. Risk Factors for Canine Osteoarthritis and Its Predisposing Arthropathies: A Systematic Review. \u003cem\u003eFront Vet Sci\u003c/em\u003e \u003cstrong\u003e7\u003c/strong\u003e, 220 (2020). https://doi.org:10.3389/fvets.2020.00220\u003c/li\u003e\n\u003cli\u003eSmith, G. K.\u003cem\u003e et al.\u003c/em\u003e Chronology of hip dysplasia development in a cohort of 48 Labrador retrievers followed for life. \u003cem\u003eVet Surg\u003c/em\u003e \u003cstrong\u003e41\u003c/strong\u003e, 20-33 (2012). https://doi.org:10.1111/j.1532-950X.2011.00935.x\u003c/li\u003e\n\u003cli\u003evan Hagen, M. A., Ducro, B. J., van den Broek, J. \u0026amp; Knol, B. W. Incidence, risk factors, and heritability estimates of hind limb lameness caused by hip dysplasia in a birth cohort of boxers. \u003cem\u003eAm J Vet Res \u003c/em\u003e\u003cstrong\u003e66\u003c/strong\u003e, 307-312 (2005). https://doi.org:10.2460/ajvr.2005.66.307\u003c/li\u003e\n\u003cli\u003eFarrar, J. T., Troxel, A. B., Stott, C., Duncombe, P. \u0026amp; Jensen, M. P. Validity, reliability, and clinical importance of change in a 0-10 numeric rating scale measure of spasticity: a post hoc analysis of a randomized, double-blind, placebo-controlled trial. \u003cem\u003eClin Ther\u003c/em\u003e \u003cstrong\u003e30\u003c/strong\u003e, 974-985 (2008). https://doi.org:10.1016/j.clinthera.2008.05.011\u003c/li\u003e\n\u003cli\u003eLascelles, B. D. X.\u003cem\u003e et al.\u003c/em\u003e Evaluation of Functional Outcome After BFX (R) Total Hip Replacement Using a Pressure Sensitive Walkway. \u003cem\u003eVet Surg\u003c/em\u003e \u003cstrong\u003e39\u003c/strong\u003e, 71-77 (2010). https://doi.org:10.1111/j.1532-950X.2009.00607.x\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"bedinvetmab, grapiprant, canis familiaris, osteoarthritis, gait analysis, noninferiority, pain management","lastPublishedDoi":"10.21203/rs.3.rs-7303674/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7303674/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA randomized, double-blinded, non-inferiority study was conducted to evaluate efficacy of bedinvetmab compared to grapiprant using objective force plate gait analysis (FPGA). Thirty-two eligible dogs (\u0026gt;\u0026thinsp;20 kg, \u0026ge; 1 year-old) with osteoarthritis (OA) exclusively at hips and/or stifles were randomized 1:1 to the licensed dose of monthly subcutaneous (SC) bedinvetmab (plus daily oral placebo) or daily oral grapiprant (plus monthly SC saline) beginning on day 0 (D0). FPGA and client-reported outcome measures (CROMs) were collected at screening, D0, and every 14 days for 2 months. Based on published FPGA parameters, success-failure rates were calculated for each group. A non-inferiority margin of 21.25% at D42 was defined a priori. FPGA treatment success rate at D42 was 68.8% for bedinvetmab and 56.3% for grapiprant, with the difference being 12.5% (90% confidence interval = -37.5, 18.8). Given that the upper bound of this interval (18.8%) was less than the pre-specified non-inferiority margin of 21.25%, bedinvetmab was concluded to be non-inferior to grapiprant. Overall, pain and associated clinical signs were significantly improved after both treatments based on CROMs. Adverse events were in line with respective label expectations. These data support both bedinvetmab and grapiprant are appropriate first-line treatments for OA pain in dogs.\u003c/p\u003e","manuscriptTitle":"A noninferiority trial evaluating the efficacy of bedinvetmab compared to grapiprant for osteoarthritis-pain in dogs using force plate gait analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-17 08:09:25","doi":"10.21203/rs.3.rs-7303674/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-21T19:44:46+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-16T15:28:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"262970198771540954021614878639140738209","date":"2025-10-01T11:57:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-01T01:11:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"192134947545739885876938644693756206941","date":"2025-09-29T14:16:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"143188336316800596003466967973103042744","date":"2025-09-29T11:21:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-28T21:03:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"161743042020890651983818445290412471915","date":"2025-09-10T09:44:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"293672065116568670291842649690297205855","date":"2025-09-09T16:32:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-09T16:29:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-03T19:21:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-14T12:08:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-08T18:02:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-08-08T17:58:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ae770458-05d9-451e-8813-b2a464e6ed88","owner":[],"postedDate":"September 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":54737693,"name":"Health sciences/Diseases"},{"id":54737694,"name":"Health sciences/Health care"},{"id":54737695,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-02-16T16:02:43+00:00","versionOfRecord":{"articleIdentity":"rs-7303674","link":"https://doi.org/10.1038/s41598-026-37626-4","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-02-10 15:59:15","publishedOnDateReadable":"February 10th, 2026"},"versionCreatedAt":"2025-09-17 08:09:25","video":"","vorDoi":"10.1038/s41598-026-37626-4","vorDoiUrl":"https://doi.org/10.1038/s41598-026-37626-4","workflowStages":[]},"version":"v1","identity":"rs-7303674","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7303674","identity":"rs-7303674","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}