Clinical and Ultrasound Remission at 48 Weeks of Upadacitinib in Rheumatoid Arthritis: Real-World Results from the Italian Multicenter UPARAREMUS Study

Clinical and Ultrasound Remission at 48 Weeks of Upadacitinib in Rheumatoid Arthritis: Real-World Results from the Italian Multicenter UPARAREMUS Study | 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 Research Article Clinical and Ultrasound Remission at 48 Weeks of Upadacitinib in Rheumatoid Arthritis: Real-World Results from the Italian Multicenter UPARAREMUS Study Andrea Picchianti Diamanti, Valentino Paci, Michele Maria Luchetti, and 17 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6812552/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Nov, 2025 Read the published version in Arthritis Research & Therapy → Version 1 posted 9 You are reading this latest preprint version Abstract Background: Achieving clinical remission is a key therapeutic goal in rheumatoid arthritis (RA). While pivotal trials and early real-world studies have demonstrated the efficacy of upadacitinib (UPA), data on its impact as assessed by imaging remain limited Here, we report the 48 weeks outcomes from the full cohort of the UPARAREMUS study. Methods: UPARAREMUS is a 12-month follow-up, observational study involving RA patients from 9 Italian rheumatology centers initiating UPA. The primary objective was to evaluate the proportion of patients achieving combined clinical and ultrasound (US) remission. Secondary endpoints included the proportion of patients achieving clinical or US remission alone at multiple time points Results: A total of 115 patients were enrolled. Combined clinical and US remission was achieved in 35% of patients at week 12, increasing to 55% at week 24 and 72% at week 48. Younger age, lower baseline CDAI, and higher ESR were associated with higher remission rates, while baseline corticosteroid use was linked to a 65% lower likelihood of achieving remission. More than 60% of patients showed absence of power Doppler (PD) signal at week 24, rising to over 80% by week 48. The majority of patients in clinical remission also achieved US remission Conclusions: After 12 months of UPA treatment, a substantial proportion of RA patients achieved combined clinical and US remission, independent of prior bDMARDs use or monotherapy. These findings highlight UPA's ability to induce and maintain deep disease control in real-world practice clinical remission ultrasonographic remission JAK inhibitors upadacitinib Figures Figure 1 Figure 2 Figure 3 Significance and Innovations This is the first study evaluating the effectiveness of UPA in patients with RA using both clinical and US remission as combined endpoints over a 12-month period After 12 months of UPA treatment, 72% of patients achieved combined clinical and US remission, underscoring its effectiveness in controlling subclinical inflammation and achieving stringent remission in a real-world RA cohort Clinical and US remission rates were comparable regardless of UPA monotherapy or prior exposure to bDMARDs. Younger age, lower CDAI, and higher ESR were positive predictors of combined remission, while corticosteroid use significantly reduced the odds of remission Introduction Effective management of rheumatoid arthritis (RA) aims to achieve remission or maintain low disease activity in order to prevent long-term joint damage and preserve both functionality and quality of life [ 1 ]. To assess remission, both clinical research and routine practice rely on various measurement tools, including Boolean-based and index-based criteria such as the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI). Additionally, the Disease Activity Score for 28 joints (DAS28), though less stringent, remains widely used in clinical settings [ 2 – 4 ]. The likelihood of achieving remission in RA varies depending on the disease-modifying antirheumatic drug (DMARD) used, the remission criteria applied, and patient-related factors such as comorbidities or disease duration, ranging around 20–40% of patients [ 5 , 6 ]. Upadacitinib (UPA) is a selective and reversible oral JAK inhibitor currently approved for the treatment of RA, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, Crohn’s disease, ulcerative colitis, and atopic dermatitis. The SELECT RA clinical trial program demonstrated the rapid and sustained efficacy of UPA in reducing RA signs and symptoms, both in combination with methotrexate and as monotherapy. Furthermore, two head-to-head trials showed that patients treated with UPA achieved significantly higher remission rates at weeks 12 and 24 compared to those treated with adalimumab or abatacept, in methotrexate-inadequate responders. These findings were consistent across different remission criteria, including DAS28, CDAI, SDAI, and Boolean-based definitions [ 7 – 9 ]. More recently, real-world data have begun to confirm the clinical effectiveness of UPA in broader patient populations [ 10 – 14 ]. These findings are particularly important, as the efficacy observed in clinical trials conducted in controlled environments and with selected patient groups may not fully reflect the heterogeneity and complexity of real-world clinical practice. However, evidence specifically addressing the impact of UPA on disease activity assessed by imaging is still limited. In fact, residual joint inflammation, detectable by ultrasonography (US) as active synovitis, can persist even in patients who fulfill clinical remission criteria [ 15 – 17 ]. This subclinical inflammation is a recognized predictor of disease flares and structural progression [ 18 – 23 ]. Baldi et al. recently demonstrated the effectiveness of UPA in 71 RA patients, showing significant improvements in both clinimetric and US parameters over 6 months [ 24 ]. In the preliminary data from the UPAdacitinib Rheumatoid Arthritis REMission UltraSonography (UPARAREMUS) study, we reported the efficacy of UPA in achieving both clinical and US remission up to 24 weeks in 60 RA patients [ 25 ]. Here, we present the 12-month outcomes from the full cohort of the UPARAREMUS study Methods Patients and Study Design This is a longitudinal 12-months follow-up observational study conducted across nine rheumathology Centres in Italy. It included consecutive RA patients classified according with the 2010 EULAR/American College of Rheumatology (ACR) criteria [ 1 ]. Participants selected were either inadequate responders to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) who had not received biologics before, referred to as bio-naïve, or patients with insufficient response to both csDMARDs and biologic DMARDs (bDMARDs), referred to as bio-failures. Inclusion Criteria Eligible patients were enrolled based on the following criteria: Male or female, aged 18 to 65 Moderate to severe disease activity, defined as a DAS28-crp score greater than 3.2 Bio-naïve patients with an inadequate response to at least six months of MTX treatment at the standard dosage, as per EULAR response criteria [ 1 ] Bio-failure patients with an inadequate response to at least six months of treatment with both MTX and bDMARDs at the standard dosage, as per EULAR response criteria [ 1 ] Exclusion Criteria Patients with contraindications to UPA as outlined in the local Summary of Product Characteristics (SmPC) Use of any bDMARDs or targeted synthetic DMARDs (tsDMARDs) other than UPA Prior exposure to tsDMARDs or bDMARDs in patients classified as bio- naïve. Ultrasonography The US evaluation was carried out by rheumatologists all expert in musculoskeletal (MS) US, all of whom had demonstrated proficiency through an interobserver reliability test. This assessment, conducted using static images on an e-learning platform, required a weighted kappa score of ≥ 0.7 to ensure consistency and accuracy. Only those meeting this standard were approved to take part in the study. To maintain objectivity, sonographers had no access to clinical data. To ensure high-quality imaging, only centers equipped with high-end US systems—such as MyLab X8 eXP, MyLab 70XVG, Logiq9, LogiqE9, or equivalent high-performance machines—were included. These devices were equipped with high-frequency probes (14–18 MHz) for optimal visualization. The severity of synovitis and PD synovitis detected via US was classified using a simplified semi-quantitative scale ranging from 0 to 3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe) [ 26 , 27 ]. For PD imaging, specific technical parameters were applied, including an 8.3–10 MHz frequency, a pulse repetition frequency of 600 Hz, and gain settings carefully adjusted to minimize noise artefacts. A low wall filter was also used. The primary focus for identifying active inflammation was PD-positive synovitis, as defined by the Outcome Measures in Rheumatology (OMERACT) criteria [ 26 ]. This lesion type is widely recognized as the most reliable marker of residual disease activity in RA and has been shown to have the highest predictive value for radiographic progression and clinical relapse compared to other US findings, such as tenosynovitis and erosions [ 17 , 23 ]. Based on our previous research, bilateral assessments were performed on two key joints: the second MCP joint and the wrist [ 17 ]. Additionally, any joints identified as swollen during clinical examination were included in the US assessment. All evaluations followed international guidelines [ 28 ]. Endpoints and Definitions The primary endpoint of the study was to establish the proportion of enrolled patients with US and clinical remission at week 24 and 48 after starting UPA treatment. Secondary endpoints were: Evaluating the percentage of patients with clinical remission according to CDAI, DAS28crp and SDAI score at weeks 12 (T1), 24 (T2), 36 (T3) and 48 (T4). Analyzing reduction in CDAI, DAS28crp and SDAI from baseline to each evaluation time (T1, T2, T3, T4) Clinical remission was defined as CDAI, DAS28crp and SDAI < 2.6, ≤ 2.8 and ≤ 3.3 respectively [ 29 – 31 ]. In order to define US remission, no joint was allowed to show a PD signal ≥ 2, whereas a PD score of 1 was permitted in no more than one joint. Ethical considerations The study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of the coordinating center (Lazio area 1, Approval numbers 6493_2021 on June 15, 2021) and by each center participating in the study; written informed consent was obtained from all the patients. Study Procedures At five key time points—baseline (T0), 12 weeks (T1), 24 weeks (T2), 36 weeks (T3), 48 weeks (T4)—the following evaluations and procedures were conducted: Collection of medical history and health status; Comprehensive clinical examination, including assessment of disease activity using DAS28-CRP, CDAI, and SDAI scores; US evaluation of both wrists and second MCP joints bilaterally, as well as any swollen joints identified during the clinical examination UPA treatment was initiated independently of study participation, based on clinical judgment and in accordance with the European Medicines Agency (EMA)’s SmPC [ 30 ]. Patients received the approved RA dosage of 15 mg once daily. Statistical Analysis All statistical analyses were performed using the R software (version 4.4.2). For descriptive analyses, categorical variables were reported as absolute numbers and frequencies, and continuous variables were expressed as median with interquartile range (IQR). Subgroup comparisons were conducted using the Mann-Whitney U test for continuous variables and Pearson’s chi-square test for categorical variables. Due to non-normal distribution, differences from baseline for continuous variables were assessed using a linear mixed model (LMM) with Bonferroni correction, accounting for repeated measures and inter-subject variability. The survival curves of the drug in each subgroup have been examined by the Kaplan-Meier method and compared statistically using a stratified log-rank test. To identify baseline predictors of US plus clinical remission, a bidirectional stepwise logistic regression was employed. The model selection was guided by minimizing the Akaike Information Criterion (AIC), with each step evaluating the inclusion or exclusion of variables. Prior to the stepwise procedure, potential multicollinearity was assessed using the Variance Inflation Factor (VIF), and variables exhibiting high multicollinearity were iteratively removed. Results were reported as Odds Ratios (ORs) with 95% confidence intervals (CI). A p-value less than 0.05 was considered significant. Results Demographic and Clinical Characteristics A total of 115 patients affected by RA were enrolled, and 94 patients completed 48-week follow-up (T4) (Table 1 ). Among the more relevant baseline data, the median disease duration was 96 months (IQR 43.5–168), 39% of patients were bio-naïve, the great majority tested positive for anti-citrullinated protein antibodies (ACPA) (72.7%) and rheumatoid factor (RF) (73.9%). Disease activity scores reflected moderate-to-high activity, with a median DAS-28crp of 4.25 (IQR: 3.75–4.94), CDAI of 23.0 (IQR: 17.0–28.5), and SDAI of 24.2 (IQR: 18.0–29.2), about half of the patients were managed with UPA in monotherapy (45.2%). Table 1 Demographic and clinical characteristics of the cohort at the baseline. Patients’ characteristics Total, n. 115 Age, years median [IQR] 56 [50.5–61] Gender (F/M), n. (%) 89 (77.4) / 26 (22.6) Comorbidities, yes n. (%) 74 (64.3) BMI, median [IQR] 24.5 [21.5–28.0] Smoke, active, n. (%) 32 (27.8) Bio-naïve, n. (%) 45 (39.1) Disease duration, months median [IQR] 96 [43.5–168] Laboratory ACPA positive, n (%) 80 (72.7) missing values: 5 RF positive, n (%) 82 (73.9) missing values: 4 CRP (mg/dl), median [IQR] 0.9 [0.5–1.77] ESR (mm/h), median [IQR] 30 [16–46] Disease Activity Tender joints, n. (%) 5 [ 3 – 8 ] Swollen joints, n. (%) 4 [ 1 – 5 ] VAS pain (0-100), median [IQR] 70 [60–80] VAS EGA (0-100), median [IQR] 60 [50–70] VAS PGA (0-100), median [IQR] 70 [50–80] DAS-28 CRP, median [IQR] 4.25 [3.75–4.94] CDAI, median [IQR] 23.0 [17.0-28.5] SDAI, median [IQR] 24.2 [18.0-29.2] Treatment Monotherapy, n (%) 52 (45.2) Combination therapy, n. (%) 63 (54.8) CCS, yes, n. (%) 68 (61.3) missing values: 4 Ultrasound PD active joints, median [IQR] 2.0 [1.0-2.5] PD grading, median [IQR] 3.0 [1.0–5.0] List of abbreviations: ACPA anti-citrullinated protein antibodies; BMI body mass index; CRP C-reactive protein; DAS 28-CRP Disease Activity Score 28 joints —C-reactive protein; RF rheumatoid factor; SD standard deviation; SDAI Simplified Disease Activity Index; CDAI Clinical Disease Activity Index; VAS Visual Analogue Scale; CCS Corticosteroids; PD Power Doppler Primary end-point Clinical plus US remission was achieved in 35% of patients at week 12 with a progressive increase to 55.7% at week 24, 63.5% at week 36 and 72.3% at week 48 (Table 2 , Fig. 1 ). Table 2 Clinical and ultrasonographic disease parameters from baseline throughout the follow-up T0 T1 T2 T3 T4 Nr. of observations 115 (100) 114 (99.1) 106 (92.2) 96 (83.5) 94 (81.7) DAS28-CRP 4.3 [3.8–4.9] 2.9 [2.1–3.6] **** 2.3 [1.7–3.2] **** 2.1 [1.4–2.8] **** 1.9 [1.3–2.6] **** CDAI 23.0 [17.0-28.5] 10.0 [5.0–17.0] **** 7.0 [3.0-12.8] **** 5.0 [2.0–9.0] **** 4.0 [1.0–8.0] **** SDAI 24.2 [18.0-29.2] 10.2 [5.0-17.3] **** 7.7 [3.5–12.9] **** 5.1 [2.3–9.5] **** 4.3 [1.2–8.3] **** VAS PAIN 70 [60–80] 40 [20–50] **** 20 [10–50] **** 20 [ 10 – 30 ] **** 20 [ 5 – 30 ] **** CRP 0.9 [0.5–1.8] 0.3 [0.1–0.7] **** 0.2 [0.1–0.6] **** 0.2 [0.1–0.4] **** 0.1 [0.1–0.4] **** PD active joints 2.0 [1.0-2.5] 0 [0.0–2.0] **** 0 [0.0–1.0] **** 0 [0.0–0.0] **** 0 [0.0–0.0] **** PD grading 3.0 [1.0–5.0] 0 [0.0–2.0] **** 0 [0.0–1.0] **** 0 [0.0–0.0] **** 0 [0.0–0.0] **** Clinical Remission 0 (0) 48 (42.1) 64 (60.4) 65 (67.7) 75 (79.8) US Remission 19 (16.5) 76 (66.7) 84 (79.2) 81 (84.4) 82 (87.2) Complete Remission 0 (0) 40 (35.1) 59 (55.7) 61 (63.5) 68 (72.3) Differences from baseline for continuous variables were assessed using a linear mixed model (LMM) with Bonferroni correction. The p -values are evaluated from T0 to every timepoint: *<0.05; **<0.01; ***<0.001; ****<0.0001. List of abbreviations: DAS 28-CRP Disease Activity Score 28 joints —C-reactive protein; SDAI Simplified Disease Activity Index; CDAI Clinical Disease Activity Index; VAS Visual Analogue Scale; PD Power Doppler Patients who achieved the primary end point were significantly younger (56 vs. 61 years, p = 0.015 ), had a shorter disease duration (79 vs. 134 months, p = 0.029 ), lower baseline CDAI scores (23.0 vs. 26.0, p = 0.045 ) and were less likely to be on corticosteroids at baseline (79.2% vs. 52.2%, p = 0.039 ) (Table 3 ). Table 3 Baseline patients’ characteristics associated with complete remission at 48 weeks Clinical and US remission after 48 weeks (T4) p value Yes (n = 70) Baseline (T0) No (n = 24) Baseline (T0) Age, years median [IQR] 56 [48.5–58.8] 61 [55.0-66.2] 0.0148 Gender (F/M), n. (%) 55 (78.6) / 15 (21.4) 18 (75.0) / 6 (25.0) 0.9374 Comorbidities, n. (%) 42 (60.0) 17 (70.8) 0.4822 BMI, median [IQR] 23.5 [21.1–27.5] 25.5 [21.5–29.6] 0.3323 Smoke, active, n. (%) 19 (27.1) 6 (25.0) 0.9500 Bio-naïve, n. (%) 32 (45.7) 7 (29.2) 0.2380 Disease duration, months median [IQR] 79 [31.5–166.0] 134 [105.0-171.0] 0.0298 Laboratory ACPA positive, n (%) 50 (74.6) missing values: 3 14 (60.9) missing values: 1 0.3225 RF positive, n (%) 53 (77.9) missing values: 2 13 (56.5) missing values: 1 0.0856 CRP (mg/dl), median [IQR] 1.1 [0.6-2.0] 0.6 [0.3–1.6] 0.1391 ESR (mm/h), median [IQR] 35 [17–52] 28 [16–37] 0.0866 Disease Activity Tender joints, n. (%) 5 [ 3 – 7 ] 6 [3.75–8.25] 0.5444 Swollen joints, n. (%) 4 [ 1 – 5 ] 5 [2.75–6.25] 0.0799 VAS pain (0-100), median [IQR] 60 [50–80] 80 [67–80] 0.0651 VAS EGA (0-100), median [IQR] 70 [50–80] 77 [70–80] 0.0806 VAS PGA (0-100), median [IQR] 60 [50–70] 70 [60–80] 0.0595 DAS-28 CRP, median [IQR] 4.12 [3.75–4.89] 4.62 [4.06–5.45] 0.0679 CDAI, median [IQR] 23.0 [17.2–26.0] 26.0 [21.9–31.5] 0.0448 SDAI, median [IQR] 24.2 [18.0-27.9] 27.0 [19.9–34.8] 0.1309 Treatment Monotherapy, n (%) 34 (48.6) 10 (41.7) 0.7279 Combination therapy, n. (%) 36 (51.4) 14 (58.3) 0.7279 CCS, yes, n. (%) 35 (52.2) missing values: 3 19 (79.2) missing values: 0 0.0392 Ultrasound PD active joints, median [IQR] 1 [1.0–2.0] 2 [1.0-2.75] 0.4511 PD grading, median [IQR] 2 [1.0–5.0] 3.5 [1.25-6.0] 0.2334 Comparison between patients who achieved clinical and US remission at 48 weeks and those who did not was assessed through Mann-Whitney U test and Pearson’s chi-square test for continuous and categorical variables, respectively. The p -value was highlighted in bold if < 0.05. List of abbreviations: ACPA anti-citrullinated protein antibodies; BMI body mass index; CRP C-reactive protein; DAS 28-CRP Disease Activity Score 28 joints —C-reactive protein; RF rheumatoid factor; SD standard deviation; SDAI Simplified Disease Activity Index; CDAI Clinical Disease Activity Index; VAS Visual Analogue Scale; CCS Corticosteroids; PD Power Doppler Factors associated with primary end point To identify baseline predictors of US plus clinical remission, a bidirectional stepwise logistic regression was performed. Younger age, lower CDAI and higher ESR levels were associated with a higher likelihood of achieving the primary end point. Specifically, each additional year in age was associated with a 5% decrease in the odds of remission (OR: 0.95, 95% CI: 0.91–0.99, p = 0.015 ), Each unit increase in CDAI was linked to a 6% reduction in the odds of remission (OR: 0.94, 95% CI: 0.89–0.99, p = 0.025 ). In contrast, each unit increase in ESR was associated with a 4% increase in the odds of remission (OR: 1.04, 95% CI: 1.01–1.06, p = 0.0026 ). Finally, patients receiving corticosteroids at baseline have 65% lower odds of achieving remission compared to those not on corticosteroids (OR: 0.35, 95% CI: 0.13–0.79, p = 0.016 ) (Table 4 ; Suppl. Materials). The great majority of patients in clinical remission had concomitant US remission at both 24 and 48 weeks (92.2% and 90.7% respectively; Fig. 3 ). Secondary end-points Clinical remission steadily increased from 0% of patients at baseline to 42% at T1, 60% at T2, 68% at T3 and 80% at T4. Sixteen percent of patients were in US remission at baseline which progressively rose to 66% at T1, 79% at T2, 84% at T3, and 87% at T4 (Table 2 ). Disease activity significantly reduced from baseline to each subsequent time point across all clinical indices, with the most substantial improvement decrease observed by week 12. Specifically, the median DAS28-CRP decreased from 4.3 at baseline to 2.9 at T1, 2.3 at T2, 2.1 at T3, and 1.9 at T4. The median CDAI and SDAI followed a similar trend, with the CDAI dropped from 23.0 to 10.0 at T1, 7.0 at T2, 5.0 at T3, and 4.0 at T4, and the SDAI declined from 24.2 at baseline to 10.2 at T1, 7.7 at T2, 5.1 at T3, and 4.3 at T4 (Fig. 2 ). Pain VAS scores showed a marked improvement, decreasing from 70 at baseline to 20 at T4, with a 50% reduction already achieved by T1. CRP levels significantly declined from 0.9 mg/dl at baseline to 0.1 mg/dl at T4, in line with the observed clinical improvements. Regarding ultrasound parameters, the median number of power doppler-active joints significantly decreased from 2.0 at baseline to 0.0 from T1 to T4. Likewise, the median PD grade was reduced from 3.0 at baseline to 0.0 throughout follow-up. Overall, more than 60% of patients exhibited complete absence of PD signal at week 24 (T2), and this proportion further increased to over 80% by week 48 (T4) (Fig. 3 ). Data collected at each follow up timing are summarised in Table 2 . Safety Discontinuations due to treatment-emergent adverse events occurred in 6 out of 155 patients (5%) in the cohort (one case each of optic neuritis, respiratory infection, and neutropenia; and three cases of recurrent herpes zoster). Seven patients (6%) discontinued upadacitinib due to inefficacy, while eight patients were considered lost to follow-up. The drug retention rate (DRR) at week 48 was 82%. Notably, main clinical and patient-related parameters—such as age, gender, BMI, disease duration, and previous exposure to bDMARDs—did not significantly influence the DRR (Fig. 4 , Suppl. Materials). Discussion This study represents the first real-life investigation assessing the effectiveness of UPA in achieving both clinical and US remission in patients with RA during a 12-month follow-up. A growing body of real-world evidence is increasingly supporting the efficacy and safety of UPA in patients with RA, as previously demonstrated in pivotal trials [ 7 – 14 , 25 ]. However, data assessing the drug’s ability to induce a deeper level of disease control, particularly when evaluated through musculoskeletal US is almost absent. In this multicentric observational study, we investigated UPA effectiveness in achieving and maintaining clinical and US remission over a 12-month period in a cohort of RA patients in a real-world setting. Our findings demonstrate that UPA, used either as monotherapy or in combination with methotrexate, in both bio-naive than bio-experienced patients, can lead to deep remission in a substantial proportion of patients. Specifically, combined clinical and US remission was observed in 35% of patients at week 12, and progressively increased to 55% by week 24 and 72% at week 48. Patients who achieved this composite outcome were significantly younger, had shorter disease duration, lower baseline CDAI scores, and were less likely to be on corticosteroids at baseline. A bidirectional stepwise logistic regression confirmed that younger age, lower CDAI, and higher ESR levels were associated with higher likelihood of achieving remission. Of note, corticosteroid use at baseline was associated with a 65% lower probability of reaching clinical and US remission. With regard to secondary outcomes, clinical remission alone was achieved in 42%, 60%, and 80% of patients at weeks 12, 24, and 48, respectively. Disease activity significantly declined from baseline across all clinical indices, with the greatest improvement observed by week 12. Clinical efficacy was corroborated by a marked reduction in synovial power doppler signal over time, with more than 60% and 80% of patients showing complete absence of PD at T2 and T4, respectively. Accordingly, only a minority of patients in clinical remission failed to achieve concomitant US remission (7.8% and 9.3% at 24 and 48 weeks, respectively). Finally, UPA demonstrated a favorable drug retention rate, with 82% of patients remaining on treatment at 48 weeks. Notably, drug retention was not adversely influenced by key clinical or lifestyle factors such as elevated BMI, smoking status, or long-standing disease. These results suggest a stringent suppression of active synovitis over time, highlighting the effectiveness of UPA not only in achieving clinical remission but also in controlling subclinical inflammation, as assessed by US. The high rate of ultrasound remission observed in our study may in part reflect the relatively favorable characteristics of our population, in which 39% of patients were bio-naïve and the remainder had failed only one or two biologics. However, logistic regression analysis confirmed that prior biologic exposure did not negatively impact the likelihood of achieving remission, supporting its broad effectiveness in real-world clinical settings. To the best of our knowledge, only three previous studies have explored the effects of UPA on both clinical and US disease activity in patients with RA. Specifically, Baldi et al. recently analyzed the efficacy and safety of UPA over a 6-month period, focusing on clinical and US parameters without assessing remission rates [ 24 ]. Significant improvements were observed in both clinimetric scores (DAS28-CRP, SDAI) and US scores (synovial hypertrophy and PD signal). Interestingly, concomitant csDMARDs therapy appeared to limit improvements in synovial hypertrophy, while higher baseline ESR or CRP levels were associated with better SDAI responses. More recently, Boyadzhieva V et al. reported a significant decrease in both gray scale and power Doppler ultrasound scores in a cohort of 53 RA patients treated with tofacitinib or upadacitinib. Notably, patients receiving upadacitinib showed a rapid and marked improvement, with a mean reduction of 10 points in gray scale, 7.2 points in power Doppler, and 10.7 points in the OMERACT composite score from baseline [ 33 ]. Our interim analysis of the UPARAREMUS study, conducted on a subgroup of patients who completed 24 weeks of treatment, showed that 63% achieved complete remission and 65% clinical remission, along with a significant reduction in both clinical disease activity parameters and US activity scores [ 25 ]. Some observational studies have also evaluated UPA's performance in achieving clinical remission using different composite indices over 6 to 12 months of follow-up in RA patients. The interim analysis of the CLOSE-UP study, conducted in a Canadian RA cohort, showed 63.5% clinical remission with DAS28-CRP, 29% with CDAI, and 26.4% with SDAI at 6 months [ 10 ]. The multicentre UPHOLD study by Ostor et al, involving a large international cohort of RA patients, reported 5% remission according to DAS28-CRP, 20% with CDAI, and 22% with SDAI at 6 months; these rates increased to 60%, and 28% at 12 months, respectively [ 11 ]. Notably, in line with our data, these studies demonstrated that remission rates were consistent regardless of UPA monotherapy or prior use of bDMARDs. Some limitations of the present study should be acknowledged. One limitation of the study is that approximately 15% of patients were already in US remission at baseline. This can be explained by the inclusion criteria, which required moderate to severe clinical disease activity, as in routine practice, but did not mandate US-confirmed synovitis. However, nearly 90% of patients in clinical remission also achieved US remission at follow-up, and we observed a consistent reduction in both the number of US-active joints and in the overall PD score, supporting the robustness of our findings. Another limitation to consider is the 12-month follow-up period, which may not fully capture the long-term safety and efficacy of UPA in real-life clinical practice. Finally, due to the real-world design of the study, the possibility of reporting or investigator bias cannot be excluded. On the other hand, the study has several strengths, including its multicenter, prospective design, the use of a homogeneous cohort of RA patients, and its innovative and more comprehensive assessment of remission, which also incorporated US evaluation. Conclusions After 12-months of treatment with UPA, 72% of patients attained the primary end-point of combined clinical and US remission. Clinical and US remission rates were comparable regardless of UPA monotherapy or prior exposure to bDMARDs. Younger age, lower baseline CDAI, and higher ESR emerged as positive predictors of remission, whereas baseline corticosteroid use, significantly reduced the likelihood of achieving the primary endpoint. These results support the effectiveness of UPA in promoting and sustaining deep disease control in patients with RA. Declarations Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethic Committee of the Coordinator Centre (Lazio area 1, Approval numbers 6493_2021 on June 15, 2021) and by each Centre participating in the study; a written informed consent was obtained from all the patients Fundings : the study has been conducted with the unconditionated support of Abbvie srl Conflicts of Interest: Andrea Picchianti Diamanti, Bruno Laganà, Annamaria Iagnocco, Marco Canzoni, Alen Zabotti, Arianna D’Antonio, Maria Sole Chimenti, Simonetta Salemi, Ilaria Bellofatto, Giorgio Sesti, Gian Domenico Sebastiani, Chiara Scirocco, Ivan Giovannnini, Michele Maria Luchetti, Valentino Paci, Gloria Crepaldi, Caterina Baldi, Paolo Falsetti, Carlo Perricone have nothing to disclose Author Contributions: Conceptualization, APD, BL, AI; methodology, APD, MC; formal analysis, VP; writing original draft, review and editing: APD, AI; IB; enrolling patients and collecting clinical data, AD, MSC, SS, GS, GMF, DF, GDS, AZ, IG, GC, MML, GF, VP, PF, CB, CS, CP Consent to Publish All authors have read and agreed to the published version of the manuscript. Data availability: The data that support the findings of this study are available from the authors databases upon reasonable request Acknowledgements Not Applicable References Smolen JS, Landewé R, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease- modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82:3–18. https:// doi. org/ 10. 1136/ ard- 2022- 223356. Verhoeven MMP, Welsing PMJ, Bijlsma JWJ, et al. Effectiveness of remission induction strategies for early rheumatoid arthritis: a systematic literature review. Curr Rheumatol Rep. 2019;21:24. https:// doi. org/ 10. 1007/ s11926- 019- 0821-1. Hamann P, Holland R, Hyrich K, et al. Factors associated with sustained remission in rheumatoid arthritis in patients treated with anti-tumor necrosis factor. Arthritis Care Res (Hoboken). 2017;69(6):783–93. https:// doi. org/ 10. 1002/ acr. 23016. Ajeganova S, Huizinga T. 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Clinical and Ultrasonographic Remission in Bio‑na.ve and Bio‑failure Patients with Rheumatoid Arthritis at 24 Weeks of Upadacitinib Treatment: The UPARAREMUS Real‑Life Study. Rheumatol Ther https://doi.org/10.1007/s40744-024-00712-y Scheel AK, Hermann K-GA, Kahler E, et al. A novel ultrasonographic synovitis scoring system suitable for analyzing finger joint inflammation in rheumatoid arthritis. Arthritis Rheum. 2005;52:733–43. https:// doi. org/ 10. 1002/ art. 20939 Szkudlarek M, Court-Payen M, Jacobsen S, et al. Interobserver agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis. Arthritis Rheum. 2003;48:955–62. https:// doi. org/ 10. 1002/ art. 10877 Bruyn AB, Iagnocco A, Naredo E, et al. OMERACT definitions for ultrasonographic pathology and elementary lesions of rheumatic disorders fifteen years on. J Rheumatol. 2019;46:10. https:// doi. org/ 10. 3899/ jrheum. 181095 Prevoo ML, Van’t Hof MA, Kuper HH, et al. Modified disease activity scores that include twentyeight- joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38:448. https:// doi. org/ 10. 1002/ art. 17803 80107. Felson D. Defining remission in rheumatoid arthritis. Ann Rheum Dis. 2012;71(Suppl 2):i86–8. https:// doi. org/ 10. 1136/annrheumdis- 2011- 200618. Smolen JS, Breedveld FC, Schiff MH, et al. A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology. 2003;42:244–57. https:// doi. org/ 10. 1093/ rheumatology/ keg072 https:// www. ema. europa. eu/ en/ medic ines/ human/EPAR/ rinvoq. Accessed 11 Aug 2024 Boyadzhieva V, Tachkov K, Emin S, Apostolova Z, Stoilov R Ultrasound Evaluation of Therapeutic Response to Tofacitinib and Upadacitinib in Patients with Rheumatoid Arthritis Real-Life Clinical Data. Biomedicines 2025, 13, 1339 https://doi.org/10.3390/biomedicines13061339 Additional Declarations No competing interests reported. Supplementary Files Fig4.jpg Cite Share Download PDF Status: Published Journal Publication published 03 Nov, 2025 Read the published version in Arthritis Research & Therapy → Version 1 posted Editorial decision: Revision requested 28 Sep, 2025 Reviews received at journal 13 Sep, 2025 Reviewers agreed at journal 31 Aug, 2025 Reviewers agreed at journal 29 Aug, 2025 Reviewers agreed at journal 17 Jul, 2025 Reviewers invited by journal 11 Jul, 2025 Editor assigned by journal 12 Jun, 2025 Submission checks completed at journal 12 Jun, 2025 First submitted to journal 03 Jun, 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. 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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-6812552","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":484928501,"identity":"d4d20c8b-9805-4805-9a71-411fd98ac143","order_by":0,"name":"Andrea Picchianti Diamanti","email":"data:image/png;base64,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","orcid":"","institution":"Department of Clinical and Molecular Medicine, \"Sapienza\" University of Rome, S. 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Andrea University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bruno","middleName":"","lastName":"Laganà","suffix":""},{"id":484928533,"identity":"3ea178b8-3785-4949-90f3-8f74712372c7","order_by":19,"name":"Annamaria Iagnocco","email":"","orcid":"","institution":"Academic Rheumatology Centre, Department of Clinical and Biological Science-University of Turin, AO Mauriziano Torino","correspondingAuthor":false,"prefix":"","firstName":"Annamaria","middleName":"","lastName":"Iagnocco","suffix":""}],"badges":[],"createdAt":"2025-06-03 14:53:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6812552/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6812552/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13075-025-03671-z","type":"published","date":"2025-11-03T15:57:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":87031011,"identity":"84e68bd3-d321-4f02-a7e3-6ffe530a2c13","added_by":"auto","created_at":"2025-07-18 12:47:23","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":51589,"visible":true,"origin":"","legend":"\u003cp\u003eHistograms representing the proportion of patients achieving the primary end-point, clinical and US remission alone, from baseline to 48 weeks. The asterisks denote the significance levels\u003c/p\u003e","description":"","filename":"Fig1copia3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6812552/v1/0a2d54f4aba6c461ca78d71d.jpg"},{"id":87031012,"identity":"dc4536ea-e539-4dae-aea0-da2f938e971b","added_by":"auto","created_at":"2025-07-18 12:47:23","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":63900,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e: Improvement in disease activity at baseline and different timepoints; \u003cstrong\u003eB:\u003c/strong\u003e Proportion of patients in clinical remission according to the different clinical indices The asterisks denote the significance levels\u003c/p\u003e","description":"","filename":"Fig2copia3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6812552/v1/72cbc637b1317b1a96cbc7a5.jpg"},{"id":87031022,"identity":"dd80c887-e2b6-4dc1-b794-35d1534f7abf","added_by":"auto","created_at":"2025-07-18 12:47:24","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":47084,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e. Pie charts depicting the proportion of patients in ultrasound (US) remission versus no US remission at T2 and T4 among those achieving clinical remission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB.\u003c/strong\u003e Distribution of max PD grades (0–3) across the entire cohort from Baseline through T4. Statistical analysis was conducted through the Friedman test followed by post-hoc comparisons between baseline and each subsequent timepoint using the Wilcoxon signed-rank test. The asterisks denote the significance levels\u003c/p\u003e","description":"","filename":"Fig3copia2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6812552/v1/e137581ab241261dd89fbf79.jpg"},{"id":95564774,"identity":"fa5238ed-1c3b-46df-9431-156719373181","added_by":"auto","created_at":"2025-11-10 16:10:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1276229,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6812552/v1/9f0e77ae-596d-4ea4-acfe-e30c7f30f94e.pdf"},{"id":87032301,"identity":"f7defdb9-dbbe-45ec-94f3-13ba571a659c","added_by":"auto","created_at":"2025-07-18 12:55:23","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":23016,"visible":true,"origin":"","legend":"","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6812552/v1/7744291f3bcde847c7a8d380.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical and Ultrasound Remission at 48 Weeks of Upadacitinib in Rheumatoid Arthritis: Real-World Results from the Italian Multicenter UPARAREMUS Study","fulltext":[{"header":"Significance and Innovations","content":"\u003cul\u003e\n \u003cli\u003eThis is the first study evaluating the effectiveness of UPA in patients with RA using both clinical and US remission as combined endpoints over a 12-month period\u003c/li\u003e\n \u003cli\u003eAfter 12 months of UPA treatment, 72% of patients achieved combined clinical and US remission, underscoring its effectiveness in controlling subclinical inflammation and achieving stringent remission in a real-world RA cohort\u003c/li\u003e\n \u003cli\u003eClinical and US remission rates were comparable regardless of UPA monotherapy or prior exposure to bDMARDs. Younger age, lower CDAI, and higher ESR were positive predictors of combined remission, while corticosteroid use significantly reduced the odds of remission\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eEffective management of rheumatoid arthritis (RA) aims to achieve remission or maintain low disease activity in order to prevent long-term joint damage and preserve both functionality and quality of life [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. To assess remission, both clinical research and routine practice rely on various measurement tools, including Boolean-based and index-based criteria such as the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI). Additionally, the Disease Activity Score for 28 joints (DAS28), though less stringent, remains widely used in clinical settings [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe likelihood of achieving remission in RA varies depending on the disease-modifying antirheumatic drug (DMARD) used, the remission criteria applied, and patient-related factors such as comorbidities or disease duration, ranging around 20\u0026ndash;40% of patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eUpadacitinib (UPA) is a selective and reversible oral JAK inhibitor currently approved for the treatment of RA, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, Crohn\u0026rsquo;s disease, ulcerative colitis, and atopic dermatitis.\u003c/p\u003e\u003cp\u003eThe SELECT RA clinical trial program demonstrated the rapid and sustained efficacy of UPA in reducing RA signs and symptoms, both in combination with methotrexate and as monotherapy. Furthermore, two head-to-head trials showed that patients treated with UPA achieved significantly higher remission rates at weeks 12 and 24 compared to those treated with adalimumab or abatacept, in methotrexate-inadequate responders. These findings were consistent across different remission criteria, including DAS28, CDAI, SDAI, and Boolean-based definitions [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMore recently, real-world data have begun to confirm the clinical effectiveness of UPA in broader patient populations [\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. These findings are particularly important, as the efficacy observed in clinical trials conducted in controlled environments and with selected patient groups may not fully reflect the heterogeneity and complexity of real-world clinical practice.\u003c/p\u003e\u003cp\u003eHowever, evidence specifically addressing the impact of UPA on disease activity assessed by imaging is still limited. In fact, residual joint inflammation, detectable by ultrasonography (US) as active synovitis, can persist even in patients who fulfill clinical remission criteria [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This subclinical inflammation is a recognized predictor of disease flares and structural progression [\u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Baldi et al. recently demonstrated the effectiveness of UPA in 71 RA patients, showing significant improvements in both clinimetric and US parameters over 6 months [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the preliminary data from the UPAdacitinib Rheumatoid Arthritis REMission UltraSonography (UPARAREMUS) study, we reported the efficacy of UPA in achieving both clinical and US remission up to 24 weeks in 60 RA patients [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHere, we present the 12-month outcomes from the full cohort of the UPARAREMUS study\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients and Study Design\u003c/h2\u003e\u003cp\u003eThis is a longitudinal 12-months follow-up observational study conducted across nine rheumathology Centres in Italy.\u003c/p\u003e\u003cp\u003eIt included consecutive RA patients classified according with the 2010 EULAR/American College of Rheumatology (ACR) criteria [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eParticipants selected were either inadequate responders to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) who had not received biologics before, referred to as bio-na\u0026iuml;ve, or patients with insufficient response to both csDMARDs and biologic DMARDs (bDMARDs), referred to as bio-failures.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInclusion Criteria\u003c/h3\u003e\n\u003cp\u003eEligible patients were enrolled based on the following criteria:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eMale or female, aged 18 to 65\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eModerate to severe disease activity, defined as a DAS28-crp score greater than 3.2\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eBio-na\u0026iuml;ve patients with an inadequate response to at least six months of MTX treatment at the standard dosage, as per EULAR response criteria [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eBio-failure patients with an inadequate response to at least six months of treatment with both MTX and bDMARDs at the standard dosage, as per EULAR response criteria [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eExclusion Criteria\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003ePatients with contraindications to UPA as outlined in the local Summary of Product Characteristics (SmPC)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eUse of any bDMARDs or targeted synthetic DMARDs (tsDMARDs) other than UPA\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePrior exposure to tsDMARDs or bDMARDs in patients classified as bio- na\u0026iuml;ve.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\n\u003ch3\u003eUltrasonography\u003c/h3\u003e\n\u003cp\u003eThe US evaluation was carried out by rheumatologists all expert in musculoskeletal (MS) US, all of whom had demonstrated proficiency through an interobserver reliability test. This assessment, conducted using static images on an e-learning platform, required a weighted kappa score of \u0026ge;\u0026thinsp;0.7 to ensure consistency and accuracy. Only those meeting this standard were approved to take part in the study. To maintain objectivity, sonographers had no access to clinical data.\u003c/p\u003e\u003cp\u003eTo ensure high-quality imaging, only centers equipped with high-end US systems\u0026mdash;such as MyLab X8 eXP, MyLab 70XVG, Logiq9, LogiqE9, or equivalent high-performance machines\u0026mdash;were included. These devices were equipped with high-frequency probes (14\u0026ndash;18 MHz) for optimal visualization. The severity of synovitis and PD synovitis detected via US was classified using a simplified semi-quantitative scale ranging from 0 to 3 (0\u0026thinsp;=\u0026thinsp;absent, 1\u0026thinsp;=\u0026thinsp;mild, 2\u0026thinsp;=\u0026thinsp;moderate, 3\u0026thinsp;=\u0026thinsp;severe) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFor PD imaging, specific technical parameters were applied, including an 8.3\u0026ndash;10 MHz frequency, a pulse repetition frequency of 600 Hz, and gain settings carefully adjusted to minimize noise artefacts. A low wall filter was also used. The primary focus for identifying active inflammation was PD-positive synovitis, as defined by the Outcome Measures in Rheumatology (OMERACT) criteria [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. This lesion type is widely recognized as the most reliable marker of residual disease activity in RA and has been shown to have the highest predictive value for radiographic progression and clinical relapse compared to other US findings, such as tenosynovitis and erosions [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eBased on our previous research, bilateral assessments were performed on two key joints: the second MCP joint and the wrist [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Additionally, any joints identified as swollen during clinical examination were included in the US assessment. All evaluations followed international guidelines [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eEndpoints and Definitions\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint of the study was to establish the proportion of enrolled patients with US and clinical remission at week 24 and 48 after starting UPA treatment.\u003c/p\u003e\u003cp\u003eSecondary endpoints were:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eEvaluating the percentage of patients with clinical remission according to CDAI, DAS28crp and SDAI score at weeks 12 (T1), 24 (T2), 36 (T3) and 48 (T4).\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eAnalyzing reduction in CDAI, DAS28crp and SDAI from baseline to each evaluation time (T1, T2, T3, T4)\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eClinical remission was defined as CDAI, DAS28crp and SDAI\u0026thinsp;\u0026lt;\u0026thinsp;2.6, \u0026le; 2.8 and \u0026le;\u0026thinsp;3.3 respectively [\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn order to define US remission, no joint was allowed to show a PD signal\u0026thinsp;\u0026ge;\u0026thinsp;2, whereas a PD score of 1 was permitted in no more than one joint.\u003c/p\u003e\n\u003ch3\u003eEthical considerations\u003c/h3\u003e\n\u003cp\u003e The study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of the coordinating center (Lazio area 1, Approval numbers 6493_2021 on June 15, 2021) and by each center participating in the study; written informed consent was obtained from all the patients.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStudy Procedures\u003c/h2\u003e\u003cp\u003eAt five key time points\u0026mdash;baseline (T0), 12 weeks (T1), 24 weeks (T2), 36 weeks (T3), 48 weeks (T4)\u0026mdash;the following evaluations and procedures were conducted:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eCollection of medical history and health status;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eComprehensive clinical examination, including assessment of disease activity using DAS28-CRP, CDAI, and SDAI scores;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eUS evaluation of both wrists and second MCP joints bilaterally, as well as any swollen joints identified during the clinical examination\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eUPA treatment was initiated independently of study participation, based on clinical judgment and in accordance with the European Medicines Agency (EMA)\u0026rsquo;s SmPC [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Patients received the approved RA dosage of 15 mg once daily.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eAll statistical analyses were performed using the R software (version 4.4.2). For descriptive analyses, categorical variables were reported as absolute numbers and frequencies, and continuous variables were expressed as median with interquartile range (IQR).\u003c/p\u003e\u003cp\u003eSubgroup comparisons were conducted using the Mann-Whitney U test for continuous variables and Pearson\u0026rsquo;s chi-square test for categorical variables.\u003c/p\u003e\u003cp\u003eDue to non-normal distribution, differences from baseline for continuous variables were assessed using a linear mixed model (LMM) with Bonferroni correction, accounting for repeated measures and inter-subject variability.\u003c/p\u003e\u003cp\u003eThe survival curves of the drug in each subgroup have been examined by the Kaplan-Meier method and compared statistically using a stratified log-rank test.\u003c/p\u003e\u003cp\u003eTo identify baseline predictors of US plus clinical remission, a bidirectional stepwise logistic regression was employed. The model selection was guided by minimizing the Akaike Information Criterion (AIC), with each step evaluating the inclusion or exclusion of variables. Prior to the stepwise procedure, potential multicollinearity was assessed using the Variance Inflation Factor (VIF), and variables exhibiting high multicollinearity were iteratively removed. Results were reported as Odds Ratios (ORs) with 95% confidence intervals (CI). A p-value less than 0.05 was considered significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eDemographic and Clinical Characteristics\u003c/h2\u003e\u003cp\u003eA total of 115 patients affected by RA were enrolled, and 94 patients completed 48-week follow-up (T4) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Among the more relevant baseline data, the median disease duration was 96 months (IQR 43.5\u0026ndash;168), 39% of patients were bio-na\u0026iuml;ve, the great majority tested positive for anti-citrullinated protein antibodies (ACPA) (72.7%) and rheumatoid factor (RF) (73.9%). Disease activity scores reflected moderate-to-high activity, with a median DAS-28crp of 4.25 (IQR: 3.75\u0026ndash;4.94), CDAI of 23.0 (IQR: 17.0\u0026ndash;28.5), and SDAI of 24.2 (IQR: 18.0\u0026ndash;29.2), about half of the patients were managed with UPA in monotherapy (45.2%).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic and clinical characteristics of the cohort at the baseline.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatients\u0026rsquo; characteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal, n.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e115\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56 [50.5\u0026ndash;61]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender (F/M), n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e89 (77.4) / 26 (22.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComorbidities, yes n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74 (64.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.5 [21.5\u0026ndash;28.0]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoke, active, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32 (27.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBio-na\u0026iuml;ve, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45 (39.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease duration, months median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96 [43.5\u0026ndash;168]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLaboratory\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACPA positive, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e80 (72.7)\u003c/p\u003e\u003cp\u003emissing values: 5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRF positive, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e82 (73.9)\u003c/p\u003e\u003cp\u003emissing values: 4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCRP (mg/dl), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.9 [0.5\u0026ndash;1.77]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eESR (mm/h), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 [16\u0026ndash;46]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDisease Activity\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTender joints, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSwollen joints, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVAS pain (0-100), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70 [60\u0026ndash;80]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVAS EGA (0-100), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60 [50\u0026ndash;70]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVAS PGA (0-100), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70 [50\u0026ndash;80]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDAS-28 CRP, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.25 [3.75\u0026ndash;4.94]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCDAI, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.0 [17.0-28.5]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSDAI, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.2 [18.0-29.2]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTreatment\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonotherapy, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52 (45.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombination therapy, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e63 (54.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCCS, yes, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68 (61.3)\u003c/p\u003e\u003cp\u003emissing values: 4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUltrasound\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePD active joints, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.0 [1.0-2.5]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePD grading, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.0 [1.0\u0026ndash;5.0]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003cem\u003eList of abbreviations: ACPA anti-citrullinated protein antibodies; BMI body mass index; CRP C-reactive protein; DAS 28-CRP Disease Activity Score 28 joints \u0026mdash;C-reactive protein; RF rheumatoid factor; SD standard deviation; SDAI Simplified Disease Activity Index; CDAI Clinical Disease Activity Index; VAS Visual Analogue Scale; CCS Corticosteroids; PD Power Doppler\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003ePrimary end-point\u003c/h2\u003e\u003cp\u003eClinical plus US remission was achieved in 35% of patients at week 12 with a progressive increase to 55.7% at week 24, 63.5% at week 36 and 72.3% at week 48 (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\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 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical and ultrasonographic disease parameters from baseline throughout the follow-up\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=\"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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eT0\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eT1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eT2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eT3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eT4\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNr. of observations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e115 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e114 (99.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e106 (92.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e96 (83.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e94 (81.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDAS28-CRP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.3 [3.8\u0026ndash;4.9]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.9 [2.1\u0026ndash;3.6] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.3 [1.7\u0026ndash;3.2] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.1 [1.4\u0026ndash;2.8] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.9 [1.3\u0026ndash;2.6] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCDAI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.0 [17.0-28.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.0 [5.0\u0026ndash;17.0]\u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.0 [3.0-12.8] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.0 [2.0\u0026ndash;9.0] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.0 [1.0\u0026ndash;8.0] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSDAI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.2 [18.0-29.2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.2 [5.0-17.3] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.7 [3.5\u0026ndash;12.9] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.1 [2.3\u0026ndash;9.5] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.3 [1.2\u0026ndash;8.3] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVAS PAIN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70 [60\u0026ndash;80]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40 [20\u0026ndash;50] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20 [10\u0026ndash;50] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e20 [\u003cspan additionalcitationids=\"CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e20 [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCRP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.9 [0.5\u0026ndash;1.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.3 [0.1\u0026ndash;0.7] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.2 [0.1\u0026ndash;0.6] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.2 [0.1\u0026ndash;0.4] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.1 [0.1\u0026ndash;0.4] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePD active joints\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.0 [1.0-2.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 [0.0\u0026ndash;2.0] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 [0.0\u0026ndash;1.0] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 [0.0\u0026ndash;0.0] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 [0.0\u0026ndash;0.0] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePD grading\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.0 [1.0\u0026ndash;5.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 [0.0\u0026ndash;2.0] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 [0.0\u0026ndash;1.0] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 [0.0\u0026ndash;0.0] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 [0.0\u0026ndash;0.0] \u003csup\u003e****\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClinical Remission\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48 (42.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64 (60.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e65 (67.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e75 (79.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUS Remission\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (16.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e76 (66.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e84 (79.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e81 (84.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e82 (87.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComplete Remission\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40 (35.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e59 (55.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e61 (63.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e68 (72.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eDifferences from baseline for continuous variables were assessed using a linear mixed model (LMM) with Bonferroni correction. The \u003cem\u003ep\u003c/em\u003e-values are evaluated from T0 to every timepoint: *\u0026lt;0.05; **\u0026lt;0.01; ***\u0026lt;0.001; ****\u0026lt;0.0001.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cem\u003eList of abbreviations: DAS 28-CRP Disease Activity Score 28 joints \u0026mdash;C-reactive protein; SDAI Simplified Disease Activity Index; CDAI Clinical Disease Activity Index; VAS Visual Analogue Scale; PD Power Doppler\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ePatients who achieved the primary end point were significantly younger (56 vs. 61 years, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.015\u003c/em\u003e), had a shorter disease duration (79 vs. 134 months, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.029\u003c/em\u003e), lower baseline CDAI scores (23.0 vs. 26.0, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.045\u003c/em\u003e) and were less likely to be on corticosteroids at baseline (79.2% vs. 52.2%, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.039\u003c/em\u003e) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\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 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline patients\u0026rsquo; characteristics associated with complete remission at 48 weeks\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=\"char\" char=\".\" 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\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eClinical \u003cem\u003eand\u003c/em\u003e US remission after 48 weeks (T4)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes (n\u0026thinsp;=\u0026thinsp;70)\u003c/p\u003e\u003cp\u003eBaseline (T0)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e\u003cp\u003eBaseline (T0)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56 [48.5\u0026ndash;58.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61 [55.0-66.2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.0148\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender (F/M), n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55 (78.6) / 15 (21.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (75.0) / 6 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.9374\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComorbidities, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (70.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.4822\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.5 [21.1\u0026ndash;27.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25.5 [21.5\u0026ndash;29.6]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.3323\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoke, active, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (27.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.9500\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBio-na\u0026iuml;ve, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32 (45.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (29.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.2380\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease duration, months median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79 [31.5\u0026ndash;166.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e134 [105.0-171.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.0298\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLaboratory\u003c/b\u003e\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\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACPA positive, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50 (74.6)\u003c/p\u003e\u003cp\u003emissing values: 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (60.9)\u003c/p\u003e\u003cp\u003emissing values: 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.3225\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRF positive, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e53 (77.9)\u003c/p\u003e\u003cp\u003emissing values: 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (56.5)\u003c/p\u003e\u003cp\u003emissing values: 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.0856\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCRP (mg/dl), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.1 [0.6-2.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.6 [0.3\u0026ndash;1.6]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.1391\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eESR (mm/h), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 [17\u0026ndash;52]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 [16\u0026ndash;37]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.0866\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDisease Activity\u003c/b\u003e\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\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTender joints, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 [\u003cspan additionalcitationids=\"CR4 CR5 CR6\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 [3.75\u0026ndash;8.25]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.5444\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSwollen joints, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 [2.75\u0026ndash;6.25]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.0799\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVAS pain (0-100), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60 [50\u0026ndash;80]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e80 [67\u0026ndash;80]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.0651\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVAS EGA (0-100), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70 [50\u0026ndash;80]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77 [70\u0026ndash;80]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.0806\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVAS PGA (0-100), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60 [50\u0026ndash;70]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70 [60\u0026ndash;80]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.0595\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDAS-28 CRP, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.12 [3.75\u0026ndash;4.89]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.62 [4.06\u0026ndash;5.45]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.0679\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCDAI, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.0 [17.2\u0026ndash;26.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26.0 [21.9\u0026ndash;31.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.0448\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSDAI, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.2 [18.0-27.9]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27.0 [19.9\u0026ndash;34.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.1309\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTreatment\u003c/b\u003e\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\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonotherapy, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34 (48.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (41.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.7279\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombination therapy, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36 (51.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (58.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.7279\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCCS, yes, n. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 (52.2)\u003c/p\u003e\u003cp\u003emissing values: 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (79.2)\u003c/p\u003e\u003cp\u003emissing values: 0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.0392\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUltrasound\u003c/b\u003e\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\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePD active joints, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 [1.0\u0026ndash;2.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 [1.0-2.75]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.4511\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePD grading, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 [1.0\u0026ndash;5.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.5 [1.25-6.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.2334\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eComparison between patients who achieved clinical \u003cem\u003eand\u003c/em\u003e US remission at 48 weeks and those who did not was assessed through Mann-Whitney U test and Pearson\u0026rsquo;s chi-square test for continuous and categorical variables, respectively. The \u003cem\u003ep\u003c/em\u003e-value was highlighted in bold if\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cem\u003eList of abbreviations: ACPA anti-citrullinated protein antibodies; BMI body mass index; CRP C-reactive protein; DAS 28-CRP Disease Activity Score 28 joints \u0026mdash;C-reactive protein; RF rheumatoid factor; SD standard deviation; SDAI Simplified Disease Activity Index; CDAI Clinical Disease Activity Index; VAS Visual Analogue Scale; CCS Corticosteroids; PD Power Doppler\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eFactors associated with primary end point\u003c/h2\u003e\u003cp\u003eTo identify baseline predictors of US plus clinical remission, a bidirectional stepwise logistic regression was performed. Younger age, lower CDAI and higher ESR levels were associated with a higher likelihood of achieving the primary end point.\u003c/p\u003e\u003cp\u003eSpecifically, each additional year in age was associated with a 5% decrease in the odds of remission (OR: 0.95, 95% CI: 0.91\u0026ndash;0.99, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.015\u003c/em\u003e), Each unit increase in CDAI was linked to a 6% reduction in the odds of remission (OR: 0.94, 95% CI: 0.89\u0026ndash;0.99, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.025\u003c/em\u003e). In contrast, each unit increase in ESR was associated with a 4% increase in the odds of remission (OR: 1.04, 95% CI: 1.01\u0026ndash;1.06, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.0026\u003c/em\u003e). Finally, patients receiving corticosteroids at baseline have 65% lower odds of achieving remission compared to those not on corticosteroids (OR: 0.35, 95% CI: 0.13\u0026ndash;0.79, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.016\u003c/em\u003e) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e; Suppl. Materials).\u003c/p\u003e\u003cp\u003eThe great majority of patients in clinical remission had concomitant US remission at both 24 and 48 weeks (92.2% and 90.7% respectively; Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003ch2\u003eSecondary end-points\u003c/h2\u003e\n\u003cp\u003eClinical remission steadily increased from 0% of patients at baseline to 42% at T1, 60% at T2, 68% at T3 and 80% at T4. Sixteen percent of patients were in US remission at baseline which progressively rose to 66% at T1, 79% at T2, 84% at T3, and 87% at T4 (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eDisease activity significantly reduced from baseline to each subsequent time point across all clinical indices, with the most substantial improvement decrease observed by week 12.\u003c/p\u003e\n\u003cp\u003eSpecifically, the median DAS28-CRP decreased from 4.3 at baseline to 2.9 at T1, 2.3 at T2, 2.1 at T3, and 1.9 at T4. The median CDAI and SDAI followed a similar trend, with the CDAI dropped from 23.0 to 10.0 at T1, 7.0 at T2, 5.0 at T3, and 4.0 at T4, and the SDAI declined from 24.2 at baseline to 10.2 at T1, 7.7 at T2, 5.1 at T3, and 4.3 at T4 (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Pain VAS scores showed a marked improvement, decreasing from 70 at baseline to 20 at T4, with a 50% reduction already achieved by T1. CRP levels significantly declined from 0.9 mg/dl at baseline to 0.1 mg/dl at T4, in line with the observed clinical improvements. Regarding ultrasound parameters, the median number of power doppler-active joints significantly decreased from 2.0 at baseline to 0.0 from T1 to T4. Likewise, the median PD grade was reduced from 3.0 at baseline to 0.0 throughout follow-up. Overall, more than 60% of patients exhibited complete absence of PD signal at week 24 (T2), and this proportion further increased to over 80% by week 48 (T4) (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eData collected at each follow up timing are summarised in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003eSafety\u003c/h2\u003e\n \u003cp\u003eDiscontinuations due to treatment-emergent adverse events occurred in 6 out of 155 patients (5%) in the cohort (one case each of optic neuritis, respiratory infection, and neutropenia; and three cases of recurrent herpes zoster). Seven patients (6%) discontinued upadacitinib due to inefficacy, while eight patients were considered lost to follow-up.\u003c/p\u003e\n \u003cp\u003eThe drug retention rate (DRR) at week 48 was 82%. Notably, main clinical and patient-related parameters\u0026mdash;such as age, gender, BMI, disease duration, and previous exposure to bDMARDs\u0026mdash;did not significantly influence the DRR (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e, Suppl. Materials).\u003c/p\u003e\n\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study represents the first real-life investigation assessing the effectiveness of UPA in achieving both clinical and US remission in patients with RA during a 12-month follow-up.\u003c/p\u003e\u003cp\u003eA growing body of real-world evidence is increasingly supporting the efficacy and safety of UPA in patients with RA, as previously demonstrated in pivotal trials [\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11 CR12 CR13\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHowever, data assessing the drug\u0026rsquo;s ability to induce a deeper level of disease control, particularly when evaluated through musculoskeletal US is almost absent.\u003c/p\u003e\u003cp\u003eIn this multicentric observational study, we investigated UPA effectiveness in achieving and maintaining clinical and US remission over a 12-month period in a cohort of RA patients in a real-world setting.\u003c/p\u003e\u003cp\u003eOur findings demonstrate that UPA, used either as monotherapy or in combination with methotrexate, in both bio-naive than bio-experienced patients, can lead to deep remission in a substantial proportion of patients. Specifically, combined clinical and US remission was observed in 35% of patients at week 12, and progressively increased to 55% by week 24 and 72% at week 48. Patients who achieved this composite outcome were significantly younger, had shorter disease duration, lower baseline CDAI scores, and were less likely to be on corticosteroids at baseline. A bidirectional stepwise logistic regression confirmed that younger age, lower CDAI, and higher ESR levels were associated with higher likelihood of achieving remission. Of note, corticosteroid use at baseline was associated with a 65% lower probability of reaching clinical and US remission.\u003c/p\u003e\u003cp\u003eWith regard to secondary outcomes, clinical remission alone was achieved in 42%, 60%, and 80% of patients at weeks 12, 24, and 48, respectively. Disease activity significantly declined from baseline across all clinical indices, with the greatest improvement observed by week 12.\u003c/p\u003e\u003cp\u003eClinical efficacy was corroborated by a marked reduction in synovial power doppler signal over time, with more than 60% and 80% of patients showing complete absence of PD at T2 and T4, respectively. Accordingly, only a minority of patients in clinical remission failed to achieve concomitant US remission (7.8% and 9.3% at 24 and 48 weeks, respectively).\u003c/p\u003e\u003cp\u003eFinally, UPA demonstrated a favorable drug retention rate, with 82% of patients remaining on treatment at 48 weeks.\u003c/p\u003e\u003cp\u003eNotably, drug retention was not adversely influenced by key clinical or lifestyle factors such as elevated BMI, smoking status, or long-standing disease. These results suggest a stringent suppression of active synovitis over time, highlighting the effectiveness of UPA not only in achieving clinical remission but also in controlling subclinical inflammation, as assessed by US. The high rate of ultrasound remission observed in our study may in part reflect the relatively favorable characteristics of our population, in which 39% of patients were bio-na\u0026iuml;ve and the remainder had failed only one or two biologics. However, logistic regression analysis confirmed that prior biologic exposure did not negatively impact the likelihood of achieving remission, supporting its broad effectiveness in real-world clinical settings.\u003c/p\u003e\u003cp\u003eTo the best of our knowledge, only three previous studies have explored the effects of UPA on both clinical and US disease activity in patients with RA.\u003c/p\u003e\u003cp\u003eSpecifically, Baldi et al. recently analyzed the efficacy and safety of UPA over a 6-month period, focusing on clinical and US parameters without assessing remission rates [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSignificant improvements were observed in both clinimetric scores (DAS28-CRP, SDAI) and US scores (synovial hypertrophy and PD signal). Interestingly, concomitant csDMARDs therapy appeared to limit improvements in synovial hypertrophy, while higher baseline ESR or CRP levels were associated with better SDAI responses.\u003c/p\u003e\u003cp\u003eMore recently, Boyadzhieva V et al. reported a significant decrease in both gray scale and power Doppler ultrasound scores in a cohort of 53 RA patients treated with tofacitinib or upadacitinib. Notably, patients receiving upadacitinib showed a rapid and marked improvement, with a mean reduction of 10 points in gray scale, 7.2 points in power Doppler, and 10.7 points in the OMERACT composite score from baseline [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur interim analysis of the UPARAREMUS study, conducted on a subgroup of patients who completed 24 weeks of treatment, showed that 63% achieved complete remission and 65% clinical remission, along with a significant reduction in both clinical disease activity parameters and US activity scores [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSome observational studies have also evaluated UPA's performance in achieving clinical remission using different composite indices over 6 to 12 months of follow-up in RA patients.\u003c/p\u003e\u003cp\u003eThe interim analysis of the CLOSE-UP study, conducted in a Canadian RA cohort, showed 63.5% clinical remission with DAS28-CRP, 29% with CDAI, and 26.4% with SDAI at 6 months [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe multicentre UPHOLD study by Ostor et al, involving a large international cohort of RA patients, reported 5% remission according to DAS28-CRP, 20% with CDAI, and 22% with SDAI at 6 months; these rates increased to 60%, and 28% at 12 months, respectively [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNotably, in line with our data, these studies demonstrated that remission rates were consistent regardless of UPA monotherapy or prior use of bDMARDs.\u003c/p\u003e\u003cp\u003eSome limitations of the present study should be acknowledged.\u003c/p\u003e\u003cp\u003eOne limitation of the study is that approximately 15% of patients were already in US remission at baseline. This can be explained by the inclusion criteria, which required moderate to severe clinical disease activity, as in routine practice, but did not mandate US-confirmed synovitis. However, nearly 90% of patients in clinical remission also achieved US remission at follow-up, and we observed a consistent reduction in both the number of US-active joints and in the overall PD score, supporting the robustness of our findings.\u003c/p\u003e\u003cp\u003eAnother limitation to consider is the 12-month follow-up period, which may not fully capture the long-term safety and efficacy of UPA in real-life clinical practice. Finally, due to the real-world design of the study, the possibility of reporting or investigator bias cannot be excluded.\u003c/p\u003e\u003cp\u003eOn the other hand, the study has several strengths, including its multicenter, prospective design, the use of a homogeneous cohort of RA patients, and its innovative and more comprehensive assessment of remission, which also incorporated US evaluation.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAfter 12-months of treatment with UPA, 72% of patients attained the primary end-point of combined clinical and US remission.\u003c/p\u003e\u003cp\u003eClinical and US remission rates were comparable regardless of UPA monotherapy or prior exposure to bDMARDs. Younger age, lower baseline CDAI, and higher ESR emerged as positive predictors of remission, whereas baseline corticosteroid use, significantly reduced the likelihood of achieving the primary endpoint. These results support the effectiveness of UPA in promoting and sustaining deep disease control in patients with RA.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethic Committee of the Coordinator Centre (Lazio area 1, Approval numbers 6493_2021 on June 15, 2021) and by each Centre participating in the study; a written informed consent was obtained from all the patients\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFundings\u003c/strong\u003e: the study has been conducted with the unconditionated support of Abbvie srl\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e Andrea Picchianti Diamanti, Bruno Lagan\u0026agrave;, Annamaria Iagnocco, Marco Canzoni, Alen Zabotti, Arianna D\u0026rsquo;Antonio, Maria Sole Chimenti, Simonetta Salemi, Ilaria Bellofatto, Giorgio Sesti, Gian Domenico Sebastiani, Chiara Scirocco, Ivan Giovannnini, Michele Maria Luchetti, Valentino Paci, Gloria Crepaldi, Caterina Baldi, Paolo Falsetti, Carlo Perricone have nothing to disclose\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e Conceptualization, APD, BL, AI; methodology, APD, MC; formal analysis, VP; writing original draft, review and editing: APD, AI; IB; enrolling patients and collecting clinical data, AD, MSC, SS, GS, GMF, DF, GDS, AZ, IG, GC, MML, GF, VP, PF, CB, CS, CP \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e The data that support the findings of this study are available from the authors databases upon reasonable request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSmolen JS, Landew\u0026eacute; R, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease- modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82:3\u0026ndash;18. https:// doi. org/ 10. 1136/ ard- 2022- 223356.\u003c/li\u003e\n\u003cli\u003eVerhoeven MMP, Welsing PMJ, Bijlsma JWJ, et al. Effectiveness of remission induction strategies for early rheumatoid arthritis: a systematic literature review. Curr Rheumatol Rep. 2019;21:24. https:// doi. org/ 10. 1007/ s11926- 019- 0821-1.\u003c/li\u003e\n\u003cli\u003eHamann P, Holland R, Hyrich K, et al. Factors associated with sustained remission in rheumatoid arthritis in patients treated with anti-tumor necrosis factor. Arthritis Care Res (Hoboken). 2017;69(6):783\u0026ndash;93. https:// doi. org/ 10. 1002/ acr. 23016.\u003c/li\u003e\n\u003cli\u003eAjeganova S, Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. Ther Adv Musculoskel Dis. 2017;9(10):249\u0026ndash;62. https:// doi. org/ 10. 1177/ 1759720X17 720366. \u003c/li\u003e\n\u003cli\u003eMesselink MA, den Broeder AA, Marinelli FE, Michgels E, Verschueren P, Aletaha D, et al. What is the best target in a treat-to-target strategy in rheumatoid arthritis? Results from a systematic review and meta-regression analysis. RMD Open. 2023;9:e003196.\u003c/li\u003e\n\u003cli\u003eTaylor PC, Moore A, Vasilescu R, Alvir J, Tarallo M. A structured literature review of the burden of illness and unmet needs in patients with rheumatoid arthritis: a current perspective. Rheumatol Int. 2016;36:685\u0026ndash;95.\u003c/li\u003e\n\u003cli\u003eStrand V, Schiff M, Tundia N, et al. Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs. Arthritis Res Ther. 2019;21:263. https:// doi. org/ 10. 1186/ s13075- 019- 2059-8.\u003c/li\u003e\n\u003cli\u003eFleischmann R, Pangan AL, Song IH, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double-blind randomized controlled trial. Arthritis Rheumatol. 2019;71(11):1788\u0026ndash;800. https:// doi.org/ 10. 1002/ art. 41032.\u003c/li\u003e\n\u003cli\u003eBurmester GR, Kremer JM, Van de Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10139):2503\u0026ndash;12. https:// doi. org/ 10. 1016/ S0140- 6736(18) 31115-2.\u003c/li\u003e\n\u003cli\u003eBessette L, Chan J, Chow A, Lisnevskaia L, Richard N et al. Real-World Effectiveness of Upadacitinib for Treatment of Rheumatoid Arthritis in Canadian Patients: Interim Results from the Prospective Observational CLOSE-UP Study. Rheumatol Ther (2024) 11:563\u0026ndash;582 https://doi.org/10.1007/s40744-024-00651-8\u003c/li\u003e\n\u003cli\u003e\u0026Ouml;st\u0026ouml;r A, Feist E, Sidiropoulos P, Avouac J, Rebella M et al. Achievement of treatment targets and maintenance of response with upadacitinib in patients with moderate-to-severe rheumatoid arthritis in real-world practice: 1-year outcomes from the UPHOLD observational study.Arthritis Research \u0026amp; Therapy\u003cem\u003e \u003c/em\u003e(2025) 27:84https://doi.org/10.1186/s13075-025-03528-5\u003c/li\u003e\n\u003cli\u003eBaldi C, Gentileschi S, Li Gobbi F, Cazzato M, Delle Sedie A et al. Real-world effectiveness and retention rate of upadacitinib in patients with rheumatoid arthritis: results from a multicentre study Clinical and Experimental Medicine (2025) 25:50 https://doi.org/10.1007/s10238-025-01578-2\u003c/li\u003e\n\u003cli\u003eYoussef P, Ciciriello S, Tahir T, Leadbetter J, Butcher B et al. Real‑World Persistence and Effectiveness of Upadacitinib versus Other Janus Kinase Inhibitors and Tumor Necrosis Factor Inhibitors in Australian Patients with Rheumatoid Arthritis. Rheumatol Ther (2025) 12:173\u0026ndash;202 https://doi.org/10.1007/s40744-024-00736-4\u003c/li\u003e\n\u003cli\u003eHayashi S, Tachibana S, Maeda T, Yamashita M, Shirasugi I et al. Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study. Rheumatology, 2024, 63, 3033\u0026ndash;3041 https://doi.org/10.1093/rheumatology/kead543\u003c/li\u003e\n\u003cli\u003eTen Cate DF, Luime JJ, Swen N, et al. Role of ultrasonography in diagnosing early rheumatoid arthritis and remission of rheumatoid arthritis - a systematic review of the literature. Arthritis Res Ther. 2013;15(1):R4. https:// doi. org/ 10. 1186/ ar4132\u003c/li\u003e\n\u003cli\u003eKawashiri SY, Suzuki T, Nakashima Y, et al. Ultrasonographic examination of rheumatoid arthritis patients who are free of physical synovitis: power Doppler subclinical synovitis is associated with bone erosion. Rheumatology (Oxford). 2014;53:562\u0026ndash;9. https:// doi. org/ 10. 1093/ rheumatology/ ket405\u003c/li\u003e\n\u003cli\u003ePicchianti Diamanti A, Navarini L, Messina F, et al. Ultrasound detection of subclinical synovitis in rheumatoid arthritis patients in clinical remission: a new reduced-joint assessment in 3 target joints. Clin Exp Rheumatol. 2018;36(6):984\u0026ndash;9\u003c/li\u003e\n\u003cli\u003eColebatch AN, Edwards CJ, \u0026Oslash;stergaard M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis.2013;72:804\u0026ndash;14. https:// doi. org/ 10. 1136/ annrheumdis- 2012- 203158\u003c/li\u003e\n\u003cli\u003eMandl P, Kurucz R, Niedermayer D, et al. Contributions of ultrasound beyond clinical data in assessing inflammatory disease activity in rheumatoid arthritis: current insights and future prospects. Rheumatology (Oxford). 2014;53:2136\u0026ndash;42. https:// doi. org/ 10. 1093/ rheum atolo gy/ keu211.\u003c/li\u003e\n\u003cli\u003eTerslev L, von der Recke P, Torp-Pedersen S, et al. Diagnostic sensitivity and specificity of Doppler ultrasound in rheumatoid arthritis. J Rheumatol. 2008;35:49\u0026ndash;53.\u003c/li\u003e\n\u003cli\u003eFilippucci E, Iagnocco A, Salaffi F, et al. Power Doppler sonography monitoring of synovial perfusion at the wrist joints in patients with rheumatoid arthritis treated with adalimumab. Ann Rheum Dis. 2006;65:1433\u0026ndash;7. https:// doi. org/ 10. 1136/ ard. 2005. 044628.\u003c/li\u003e\n\u003cli\u003eNaredo E, Moller I, Cruz A, et al. Power Doppler ultrasonographic monitoring of response to anti-tumor necrosis factor therapy in patients with rheumatoid arthritis. Arthritis Rheum. 2008;58:2248\u0026ndash;56. https:// doi. org/ 10. 1002/ art. 23682\u003c/li\u003e\n\u003cli\u003eSilvagni E, Zandonella Callegher S, et al. Musculoskeletal ultrasound for treating rheumatoid arthritis to target\u0026mdash;a systematic literature review. Rheumatology. 2022;61:4590\u0026ndash;602.\u003c/li\u003e\n\u003cli\u003eBaldi C, Parisi S, Falsetti P, Sota S, Ditto MC et al. Efficacy and Safety of Upadacitinib in Rheumatoid Arthritis: Real-Life Experience from a Prospective Longitudinal Multicentric Study. J. Clin. Med. 2024, 13, 401. https://doi.org/10.3390/jcm13020401\u003c/li\u003e\n\u003cli\u003ePicchianti Diamanti A, Cattaruzza MS, Salemi S, Di Rosa R, Sesti G et al. Clinical and Ultrasonographic Remission in Bio‑na.ve and Bio‑failure Patients with Rheumatoid Arthritis at 24 Weeks of Upadacitinib Treatment: The UPARAREMUS Real‑Life Study. Rheumatol Ther https://doi.org/10.1007/s40744-024-00712-y\u003c/li\u003e\n\u003cli\u003eScheel AK, Hermann K-GA, Kahler E, et al. A novel ultrasonographic synovitis scoring system suitable for analyzing finger joint inflammation in rheumatoid arthritis. Arthritis Rheum. 2005;52:733\u0026ndash;43. https:// doi. org/ 10. 1002/ art. 20939\u003c/li\u003e\n\u003cli\u003eSzkudlarek M, Court-Payen M, Jacobsen S, et al. Interobserver agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis. Arthritis Rheum. 2003;48:955\u0026ndash;62. https:// doi. org/ 10. 1002/ art. 10877\u003c/li\u003e\n\u003cli\u003eBruyn AB, Iagnocco A, Naredo E, et al. OMERACT definitions for ultrasonographic pathology and elementary lesions of rheumatic disorders fifteen years on. J Rheumatol. 2019;46:10. https:// doi. org/ 10. 3899/ jrheum. 181095\u003c/li\u003e\n\u003cli\u003ePrevoo ML, Van\u0026rsquo;t Hof MA, Kuper HH, et al. Modified disease activity scores that include twentyeight- joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38:448. https:// doi. org/ 10. 1002/ art. 17803 80107.\u003c/li\u003e\n\u003cli\u003eFelson D. Defining remission in rheumatoid arthritis. Ann Rheum Dis. 2012;71(Suppl 2):i86\u0026ndash;8. https:// doi. org/ 10. 1136/annrheumdis- 2011- 200618.\u003c/li\u003e\n\u003cli\u003eSmolen JS, Breedveld FC, Schiff MH, et al. A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology. 2003;42:244\u0026ndash;57. https:// doi. org/ 10. 1093/ rheumatology/ keg072\u003c/li\u003e\n\u003cli\u003ehttps:// www. ema. europa. eu/ en/ medic ines/ human/EPAR/ rinvoq. Accessed 11 Aug 2024\u003c/li\u003e\n\u003cli\u003eBoyadzhieva V, Tachkov K, Emin S, Apostolova Z, Stoilov R Ultrasound Evaluation of Therapeutic Response to Tofacitinib and Upadacitinib in Patients with Rheumatoid Arthritis Real-Life Clinical Data. Biomedicines 2025, 13, 1339 https://doi.org/10.3390/biomedicines13061339\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":"arthritis-research-and-therapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arrt","sideBox":"Learn more about [Arthritis Research \u0026 Therapy](http://arthritis-research.biomedcentral.com/)","snPcode":"13075","submissionUrl":"https://submission.nature.com/new-submission/13075/3","title":"Arthritis Research \u0026 Therapy","twitterHandle":"@ArthritisRes","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"clinical remission, ultrasonographic remission, JAK inhibitors, upadacitinib","lastPublishedDoi":"10.21203/rs.3.rs-6812552/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6812552/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Achieving clinical remission is a key therapeutic goal in rheumatoid arthritis (RA). While pivotal trials and early real-world studies have demonstrated the efficacy of upadacitinib (UPA), data on its impact as assessed by imaging remain limited Here, we report the 48 weeks outcomes from the full cohort of the UPARAREMUS study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e UPARAREMUS is a 12-month follow-up, observational study involving RA patients from 9 Italian rheumatology centers initiating UPA. The primary objective was to evaluate the proportion of patients achieving combined clinical and ultrasound (US) remission. Secondary endpoints included the proportion of patients achieving clinical or US remission alone at multiple time points\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e A total of 115 patients were enrolled. Combined clinical and US remission was achieved in 35% of patients at week 12, increasing to 55% at week 24 and 72% at week 48. Younger age, lower baseline CDAI, and higher ESR were associated with higher remission rates, while baseline corticosteroid use was linked to a 65% lower likelihood of achieving remission. More than 60% of patients showed absence of power Doppler (PD) signal at week 24, rising to over 80% by week 48. The majority of patients in clinical remission also achieved US remission\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e After 12 months of UPA treatment, a substantial proportion of RA patients achieved combined clinical and US remission, independent of prior bDMARDs use or monotherapy. These findings highlight UPA's ability to induce and maintain deep disease control in real-world practice\u003c/p\u003e","manuscriptTitle":"Clinical and Ultrasound Remission at 48 Weeks of Upadacitinib in Rheumatoid Arthritis: Real-World Results from the Italian Multicenter UPARAREMUS Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-18 12:47:19","doi":"10.21203/rs.3.rs-6812552/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-28T10:02:07+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-13T06:27:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"323392511031558523929865183024585191305","date":"2025-08-31T20:04:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"211618899437599249285134861739591985007","date":"2025-08-29T20:06:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"43896853586953278057037416938253257423","date":"2025-07-17T07:38:08+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-11T18:49:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-12T21:58:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-12T04:36:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"Arthritis Research \u0026 Therapy","date":"2025-06-03T14:40:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"arthritis-research-and-therapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arrt","sideBox":"Learn more about [Arthritis Research \u0026 Therapy](http://arthritis-research.biomedcentral.com/)","snPcode":"13075","submissionUrl":"https://submission.nature.com/new-submission/13075/3","title":"Arthritis Research \u0026 Therapy","twitterHandle":"@ArthritisRes","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"98693d57-51f3-49fd-a604-6f8774d8d927","owner":[],"postedDate":"July 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-10T16:09:28+00:00","versionOfRecord":{"articleIdentity":"rs-6812552","link":"https://doi.org/10.1186/s13075-025-03671-z","journal":{"identity":"arthritis-research-and-therapy","isVorOnly":false,"title":"Arthritis Research \u0026 Therapy"},"publishedOn":"2025-11-03 15:57:50","publishedOnDateReadable":"November 3rd, 2025"},"versionCreatedAt":"2025-07-18 12:47:19","video":"","vorDoi":"10.1186/s13075-025-03671-z","vorDoiUrl":"https://doi.org/10.1186/s13075-025-03671-z","workflowStages":[]},"version":"v1","identity":"rs-6812552","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6812552","identity":"rs-6812552","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}