Clinical, Radiological and Pharmacokinetic Data of CT-P13 Subcutaneous in Fistulizing Anoperineal Lesions of Crohn’s Disease

Clinical, Radiological and Pharmacokinetic Data of CT-P13 Subcutaneous in Fistulizing Anoperineal Lesions of Crohn’s Disease | 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, Radiological and Pharmacokinetic Data of CT-P13 Subcutaneous in Fistulizing Anoperineal Lesions of Crohn’s Disease Nadia Fathallah, Mélanie Draulette, Julien Kirchgesner, Stéphane Paul, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6264439/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Jul, 2025 Read the published version in Digestive Diseases and Sciences → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose The aim of this study was to evaluate the clinico-radiological remission rate in patients with fistulizing anoperineal lesions of Crohn's disease treated with CT-P13 SC, as well as pharmacokinetic data and treatment persistence rate. Methods We included all consecutive patients seen in the dedicated proctology outpatient clinic between June 1st and July 15th, 2024, for fistulizing anoperineal lesions and treated for at least 3 months with CT-P13 SC. Clinical, radiological and pharmacokinetic data were collected. Results Data from 39 patients were analyzed. The median duration of treatment was 16.1 months. Seventeen patients (43.6%) had received SC formulation from the start. The complete clinical remission rate was 74.4%, significantly higher in patients switched from IV to SC formulation. The deep radiological remission rate was 61.5%. The median infliximab concentration was 22.7 µg/mL. Only the intensified administration protocol impacted infliximab concentration. Immunosuppressants had no impact. The median infliximab concentration was higher in patients in remission (35.9 µg/mL versus 22.4 µg/mL), but without any significant difference. Among patients switched from IV to SC formulation, 86.5% maintained remission. In the overall study population, 89.7% were able to continue treatment, with intensified protocols in 61.5% of patients. Conclusion CT-P13 SC appears to be at least as effective as the IV formulation for fistulizing anoperineal lesions. Switching from IV to SC formulation seems more effective in achieving clinical remission. Despite numerically higher infliximab concentrations in patients in remission, no significant difference could be identified. Switching from IV to SC formulation was associated with maintenance of remission in 86.5% of cases. Crohn’s disease Infliximab CT-P13 SC Anoperineal lesions Anal fistulas Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction The recommendations of the European Crohn's and Colitis Organisation (ECCO) [1] and the French National Society of Coloproctology (SNFCP) [2] indicate infliximab as the first-line treatment for perianal lesions (PAL) in Crohn's disease, following the work of Present et al. and the ACCENT II study [3-4]. A subcutaneous formulation of infliximab (CT-P13 SC) has been developed for maintenance therapy, offering the possibility of self-administration [5-6]. In 2020, this formulation received regulatory approval from the European Medicines Agency (EMA) for all previously approved indications of intravenous (IV) infliximab, including inflammatory bowel diseases [7]. The phase 3 randomized controlled trial Liberty demonstrated the efficacy of CT-P13 SC versus placebo specifically in luminal Crohn’s disease. After 56 weeks of follow-up, the rate of complete clinical remission was 62.3% compared to 32.1% (p < 0.0001), and the rate of endoscopic response was 51.1% compared to 17.9% (p < 0.0001). The safety profile was also favorable [8]. In another randomized controlled non-inferiority trial, pharmacokinetic data, efficacy, safety, and immunogenicity appeared similar between the IV and SC formulations [6]. In the Remswitch study, switching from IV to SC infliximab at 120 mg every 2 weeks maintained luminal remission in the vast majority of patients; only those previously receiving infliximab IV at 10 mg/kg every 4 weeks required therapeutic intensification to 240 mg every 2 weeks [9]. Regarding pharmacokinetic monitoring, unlike IV infliximab, the concentration of the SC formulation appears to remain stable between injections, allowing for simplified monitoring that can be performed at any time between doses [10]. Additionally, similar to residual levels of IV infliximab, high serum infliximab concentrations (> 20 µg/ml) with the SC formulation were associated with higher rates of long-term clinical remission, with a sensitivity of 0.91, specificity of 0.80, and accuracy of 0.85. Finally, concomitant immunosuppressive therapy did not appear to impact pharmacokinetic measurements [11]. In the specific case of PAL, high residual serum levels of intravenous infliximab (>10.10 mg/L), or even above 20 mg/L, also appear to be preferable in terms of efficacy [12]. Patients are often treated with intensified protocols of 10 mg/kg every 6 weeks, or even every 4 weeks [13]. To date, there is no specific publication regarding the use of CT-P13 SC in Crohn’s disease PAL. Therefore, the aim of our study was to assess its efficacy in the treatment of fistulizing PAL and its correlation with pharmacokinetic data. Patients and Methods Study Design and Data Collection We included all consecutive patients over 18 years of age who were seen in a dedicated medical-surgical proctology outpatient clinic between June 1st and July 15th, 2024, in two French centers (Saint-Joseph Hospital and Saint-Antoine Hospital in Paris). Eligible patients had been treated with CT-P13 SC for at least 3 months and presented with fistulizing PAL associated with Crohn’s disease. The 3-month treatment duration criterion was established in order to reach a minimum sample size of 30 patients. During this period, patients who had previously received CT-P13 but discontinued it due to treatment failure were also documented. We collected demographic data, including age, sex, weight, smoking status, disease extent and phenotype, history of proctologic interventions, Harvey-Bradshaw Index score, fecal calprotectin levels, and data on luminal remission as assessed by the most recent colonoscopy performed prior to the consultation. The CT-P13 SC treatment regimen was categorized as follows: standard : 120 mg every 2 weeks intensified : 120 mg weekly or 240 mg every 2 weeks The initiation scheme was also differentiated as: initiated upfront : immediately after 2 or 3 standard IV infusions (Week 0, Week 2, Week 6) a switch from a previous IV maintenance phase The dose, frequency, and duration of prior IV infliximab treatment were specified. The clinical status of perianal disease at the time of CT-P13 SC initiation was recorded (remission/active disease). It is important to note that no patients with complete failure of IV infliximab therapy were transitioned to CT-P13 SC. Definition of Evaluation Criteria The clinical proctological evaluation of the anoperineal area was performed by a specialized surgical proctologist on the day of inclusion in each of the two centers. Clinical outcomes were defined as follows: Complete clinical remission corresponded to the closure of all external fistula openings, without pain, discharge under pressure, or abscesses. Clinical response corresponded to partial closure of the external fistula openings and/or a decrease in pain and discharge under pressure, without abscesses. Treatment failure corresponded to the absence of a clinical response and/or the development of a new abscess and/or fistula. The PDAI score was also calculated for all patients. Radiological assessment was based on data from an anoperineal MRI performed at least 3 months after the initiation of CT-P13 SC therapy. All MRIs were reviewed by a radiologist specialized in APL related to Crohn’s disease in each of the two centers. The Magnifi-CD score was calculated. Radiological remission was defined as a Magnifi-CD score < 6 [14]. Deep combined clinico-radiological remission was defined as the association of complete clinical remission with radiological remission. On the day of the consultation, patients underwent blood sampling for pharmacokinetic tests (serum infliximab levels and anti-infliximab antibodies testing), as well as fecal calprotectin measurement. Pharmacokinetic Sampling Technique Infliximab serum levels were measured using an automated enzyme-linked immunosorbent assay (ELISA) (i-Track10, Theradiag, Marne La Vallée, France) as per the manufacturer’s instructions. The samples were diluted with the kit assay buffer at either 1:20, 1:10 or 1:4 as required, and the concentration was determined from the standard curve multiplied by the dilution factor. The upper limit of the assay was 24 μg/ml and the lower limit of quantification was 0,3 μg/ml. Given the assay used in our institution is drug-sensitive, Assessment for anti-drug antibodies was only performed on samples with a drug level < 0,5 μg/ml. Therapeutic Management Based on Clinico-Radiological and Pharmacokinetic Data Patients were contacted 3 months after the inclusion visit to determine the subsequent therapeutic management, taking into account clinico-radiological and pharmacokinetic data. Study Objectives The primary endpoint was the rate of deep clinico-radiological remission of fistulizing APL under CT-P13 SC at the inclusion visit. Secondary endpoints were: Luminal disease data Pharmacokinetic data and their association with deep clinico-radiological remission The persistence rate of CT-P13 SC treatment from initiation until the 3-month follow-up visit Ethics The study was approved by the ethics committee of Saint-Joseph Hospital (IRB 00012157), and all patients signed an information and non-opposition form for the collection of their data. Funding The study was partially funded by Celltrion Laboratories to cover the costs of pharmacokinetic assays, which are not reimbursed by the French national health insurance system. The study’s primary sponsor was Saint-Joseph Hospital, which was responsible for data centralization and statistical analysis. Statistics Statistical analyses were performed using R software (v4.3.2). Continuous variables were expressed as median and interquartile range [IQR] or as mean ± standard deviation, according to their distribution assessed by the Shapiro-Wilk test. Comparisons between groups were performed using the Mann-Whitney test for non-parametric continuous variables and Student’s t-test for normally distributed variables. Categorical variables were compared using the chi-square test or Fisher’s exact test when expected counts were less than 5. The association between serum infliximab levels and deep clinico-radiological remission was assessed using Spearman’s correlation analysis. Univariate and multivariate logistic regression analyses were performed to identify predictors of deep clinico-radiological remission, adjusting for relevant variables (age, surgical history, SC initiation versus IV switch, infliximab serum levels, etc.). Results were reported as odds ratios (OR) with their 95% confidence intervals (95% CI). Treatment persistence was assessed using Kaplan-Meier survival analysis, with survival curves compared by the log-rank test. A p-value < 0.05 was considered statistically significant for all analyses. Results Study Population During the study period, 43 patients with fistulizing APL associated with Crohn’s disease were treated with CT-P13 SC. Three patients were not included because they had received less than 3 months of treatment. During the study period, no patients seen in consultation had previously been treated with CT-P13 SC and discontinued due to treatment failure. In total, 40 patients were included in the study. However, one patient was excluded from the analysis because she was in early pregnancy at the time of sampling (Figure 1). Fistulizing APL was complex in 38 patients, including 2 cases of rectovaginal fistulas. Three patients had associated ulcerated anal involvement, and four patients had associated stenosing disease. Table 1 describes the study population. Description of CT-P13 SC Treatment CT-P13 SC treatment was prescribed as follows: Initiated upfront in 17 patients As a switch from IV infliximab in 22 patients, with a median time between the switch from IV to SC of 61.6 months [22.4–142.4]. All patients who received CT-P13 SC as an upfront treatment had active APL. In this group, during follow-up, 11 patients initially treated with standard doses of CT-P13 SC required intensification to 120 mg weekly due to partial clinical response of the APL. Among the patients who switched from IV to CT-P13 SC, 20 were in complete remission and 2 in partial response. Of those who were on intensified IV maintenance therapy, 50% were immediately transitioned to intensified CT-P13 SC protocols. Table 2 details the treatment protocols at the time of the inclusion visit. Deep Clinico-Radiological Remission Rate of APL At the time of evaluation, after a median duration of CT-P13 SC treatment of 16.1 months [10.3–25.7], 29 patients (74.4%) were in complete clinical remission, 3 patients (7.7%) were in partial remission, and 7 patients (17.9%) were considered treatment failures (Table 3) (Figure 2). The complete clinical remission rate was 64.7% in patients who initiated SC treatment upfront and 81.8% in those who switched from IV therapy (OR [95% CI] = 4.3 [1.1–17.9], p = 0.042), with no statistically significant difference in treatment exposure duration: 12.7 months (6.0; 36.7) [9.0–25.1] versus 19.5 [14.0–23.3] (p = 0.203) (Table 3). The median PDAI score was 0.5 [0–4]. Finally, the median Magnifi-CD score was 0 [0–10], and 24 patients had a Magnifi-CD score < 6. The deep clinico-radiological remission rate was therefore 61.5% (Figure 3). It is reported according to the administration protocol in Table 4. Luminal Disease Data The median Harvey-Bradshaw Index score was 1 [0–4], with no significant difference between patients with or without deep anoperineal clinico-radiological remission (1 [0.0–3.3] versus 2 [0.5–5.0], p = 0.418). Twenty-three patients (59.0%) were in complete luminal remission: 16 patients (66.7%) in the group with deep anoperineal clinico-radiological remission versus 7 patients (46.7%) in the group without remission (p = 0.157). The median fecal calprotectin level was 79.2 µg/g [35.5–133.0], with no difference between patients with or without deep anoperineal clinico-radiological remission (79.2 µg/g [50.0–116.0] versus 80.0 µg/g [45.0–115.0]). Pharmacokinetic Data The median infliximab concentration was 22.7 µg/ml [19.3–38.6]. It was < 23 µg/ml in 20 patients and ≥ 24 µg/ml in 19 patients. Among patients with infliximab concentrations ≥ 24 µg/ml, the median was 40 µg/ml [36.9–46.5], and one patient reached a concentration of 80.8 µg/ml. Anti-infliximab antibodies associated with an infliximab concentration < 0.3 µg/ml were detected in 2 patients. One of these 2 patients had previously received IV therapy before switching to SC and did not have antibodies at that time. The intensified CT-P13 SC administration protocol was significantly associated with a higher infliximab concentration (OR = 16.7 [27.4–6.0], p = 0.004). The use of concomitant immunosuppressive therapy, demographic data, and the administration protocol (upfront SC versus switch from IV) were not associated with infliximab concentration levels. Association Between Pharmacokinetic Data and Deep Clinico-Radiological Remission The median infliximab concentration was 35.9 µg/ml [20.2–41.5] in patients in remission versus 22.4 µg/ml [16.5–36] in patients without remission, but the difference was not statistically significant (p = 0.184). Treatment Persistence Therapeutic management of patients, based on clinical, radiological response and pharmacokinetic data, is summarized in Table 5. A change in therapy was considered in 4 out of 7 patients with clinical failure: 2 patients had a partial response to IV infliximab and subsequently failed intensified CT-P13 SC (infliximab concentration > 24 µg/ml without antibodies); 1 patient was in complete remission with IV therapy and became active after switching to SC, with an infliximab concentration 24 µg/ml without antibodies). Therapeutic intensification was considered in 3 patients: 2 patients with treatment failure in the CT-P13 SC upfront group (infliximab concentration < 24 µg/ml without antibodies); 1 patient with partial response in the CT-P13 SC upfront group (infliximab concentration < 0.3 µg/ml with antibodies at 28 µg/ml). Azathioprine was also added to the treatment regimen. The treatment was not modified in 3 patients, at their request despite the absence of remission: 1 patient with failure of CT-P13 SC initiated upfront with the standard protocol, infliximab concentration at 22.7 µg/ml without antibodies; 2 patients with partial response (1 in the CT-P13 SC upfront group and 1 switched from IV therapy), both under the standard protocol with infliximab concentration > 24 µg/ml. In the end, after a median duration of 16.1 months [10.3–25.7] of CT-P13 SC treatment, 24 patients (61.5%) were receiving an intensified dose. This protocol had been initiated from the start in 10 patients who had switched from intensified IV therapy and was subsequently adjusted according to the clinico-radiological response ± pharmacokinetic data in the other patients (11 before the inclusion visit and 3 afterwards). CT-P13 SC treatment was discontinued in 4 out of 39 patients (10.3%). Among patients who switched from IV to SC, 86.4% maintained their treatment. Figure 4 shows the probability of survival without therapeutic change in patients with APL treated with CT-P13 SC. Discussion We conducted the first prospective, bicentric study assessing the clinico-radiological response and its correlation with pharmacokinetic data in patients with fistulizing APL treated with CT-P13 SC. More than two-thirds of patients were receiving infliximab as first-line therapy. After a median exposure of 16 months to CT-P13 SC, the deep clinico-radiological remission rate was 61.5%. In addition, the complete clinical remission rate was 74.4%. If we consider the pivotal studies on IV infliximab [3-4], the efficacy of the SC formulation appears to be superior. However, in real-life settings, the efficacy of IV infliximab combined with surgical treatment of APL varies from 47% to 88%, which is more consistent with our findings [15-17]. The recurrence rate after switching from IV to SC formulation was low in our cohort and consistent with data from the literature. Among patients who switched from IV to SC, 86.4% were able to continue treatment. Only one patient experienced disease progression after having been in remission under IV therapy, while the two other patients already had a partial response on IV infliximab. The overall CT-P13 SC treatment persistence rate, considering both protocols (upfront initiation/switch from IV), was excellent at 89.7%. In a series of 181 patients with inflammatory bowel disease treated with CT-P13 SC, 2 out of 25 patients with Crohn’s disease-related APL experienced recurrence [18]. In another series including only 9 patients with APL, none showed disease progression [19]. In our cohort, patients initially treated with IV infliximab before switching to the SC formulation achieved higher rates of clinical remission compared to those who received SC treatment upfront. However, this difference disappeared when considering deep clinico-radiological remission, although the numerical rates remained higher (66.7% after IV switch versus 33.3% with upfront SC treatment), likely due to limited statistical power. It is important to note that the vast majority of patients had severe APL and that 90.9% were receiving intensified IV infliximab protocols prior to switching. Moreover, no data from the existing literature currently support such a treatment sequence in APL. Regarding pharmacokinetic data, Roblin et al. demonstrated that a cut-off infliximab concentration of 20 µg/ml was necessary to achieve deep luminal remission [11]. It is also well known that APL requires high residual IV infliximab levels [12]. In our cohort, the median infliximab concentration was elevated at 22.7 µg/ml [19.3–38.6], and it was ≥ 24 µg/ml in 48.7% of patients. Neutralizing anti-infliximab antibodies were detected in only 5.1% of patients, consistent with previously reported low rates [20-21]. Immunosuppressants did not appear to impact the pharmacokinetics of the SC formulation, in contrast to what has been observed with IV infliximab [20-21]. However, although infliximab concentrations were higher in patients achieving deep clinico-radiological remission compared to those who did not, there was no statistically significant difference in our series—likely due to limited statistical power and the large proportion of patients (53.8%) already on intensified SC protocols. Our study has two main limitations: the limited number of patients, which is explained by the high cost of pharmacokinetic testing, and the absence of long-term follow-up under treatment., et l’absence de suivi prolongé sous traitement. Conclusion This study in patients treated with CT-P13 SC for complex fistulizing APL demonstrated a deep clinico-radiological remission rate of 61.5%, with an intensified treatment protocol in more than half of the cases. There was no significant correlation between pharmacokinetic data and deep remission, although infliximab concentrations were higher in patients in remission. Interestingly, patients initially treated with IV infliximab and subsequently switched to SC therapy appeared more likely to achieve complete clinical remission. Finally, the treatment persistence rate was 89.7%, and only 13.6% of patients experienced disease progression after switching from IV to SC. These preliminary results are promising but will, of course, need to be confirmed by further studies. Abbreviations CT-P13 SC subcutaneous infliximab PAL Perianal lesions IV intravenous SC subcutaneous Declarations Disclosures and declarations: Competing interests Nadia Fathallah: received consulting fees from Takeda, lecture fees from Abbvie, Celltrion, Tillots, Janssen, Amgen, Viatris and Sandoz. Vincent de Parades: received consulting fees from Takeda and Abbvie, lectures fees from Amgen, Janssen, Sandoz, Takeda, Tillots. Julien Kirchgesner: received lecture fees from Celltrion, Lilly, and Janssen; consulting fees from Abbvie, Alfasigma, Amgen, Celltrion, Janssen, Takeda, Tillots, and Pfizer. Mohamed Amine Haouari: received lecture fees from Takeda. Edouard Chambenois: received lecture fees from Amgen, Viatris and Mylan. Stéphane Paul : no competing interests. Xavier Roblin : received lecture fees from Celltrion, Lilly, and Janssen ; consulting fees from Abbvie, Alfasigma, Amgen, Celltrion, Janssen, Takeda, Tillots, and Pfizer. Mélanie Draulette : no competing interests. Anne Bourrier : received lecture fees from Ferring and Janssen Philippe Seksik : received consulting fees from Takeda, Abbvie, Merck-MSD, Biocodex, Janssen, Amgen, Astellas and Pfizer and grants from Biocodex and Janssen. Aknowledgment: We would like to thank the clinical research centers of Saint-Joseph and Saint-Antoine for their help in carrying out this project Data Transparency: Data are valid upon online request on a secure REDCAP site Trial registration number and date : Registration with the ethics committee on 11/14/2023. References Torres J, Bonovas S, Doherty G, Kucharzik T, Gisbert JP, Raine T, Adamina M, Armuzzi A, Bachmann O, Bager P, Biancone L, Bokemeyer B, Bossuyt P, Burisch J, Collins P, El-Hussuna A, Ellul P, Frei-Lanter C, Furfaro F, Gingert C, Gionchetti P, Gomollon F, González-Lorenzo M, Gordon H, Hlavaty T, Juillerat P, Katsanos K, Kopylov U, Krustins E, Lytras T, Maaser C, Magro F, Marshall JK, Myrelid P, Pellino G, Rosa I, Sabino J, Savarino E, Spinelli A, Stassen L, Uzzan M, Vavricka S, Verstockt B, Warusavitarne J, Zmora O, Fiorino G (2020) ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis 14 :4-22. https://doi.org/10.1093/ecco-jcc/jjz180. Bouchard D, Pigot F, Staumont G, Siproudhis L, Abramowitz L, Benfredj P, Brochard C, Fathallah N, Faucheron JL, Higuero T, Panis Y, de Parades V, Vinson-Bonnet B, Laharie D (2018) Management of anoperineal lesions in Crohn's disease: a French National Society of Coloproctology national consensus. Tech Coloproctol 22:905-917. https://doi.org/10.1007/s10151-018-1906-y. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, Podolsky DK, Sands BE, Braakman T, DeWoody KL, Schaible TF, van Deventer SJ (1999) Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 340:1398-405. https://doi.org/10.1056/NEJM199905063401804. Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ (2004) Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl 350:876-85. https://doi.org/10.1056/NEJMoa030815. Parigi TL, D'Amico F, Peyrin-Biroulet L, Danese S. Evolution of infliximab biosimilar in inflammatory bowel disease: from intravenous to subcutaneous CT-P13 (2021) Expert Opin Biol Ther 21:37-46. https://doi.org/10.1080/14712598.2020.1811849. Schreiber S, Ben-Horin S, Leszczyszyn J, Dudkowiak R, Lahat A, Gawdis-Wojnarska B, Pukitis A, Horynski M, Farkas K, Kierkus J, Kowalski M, Lee SJ, Kim SH, Suh JH, Kim MR, Lee SG, Ye BD, Reinisch W (2021) Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease. Gastroenterology 160:2340-2353. https://doi.org/10.1053/j.gastro.2021.02.068. European Medicines Agency Remsima. European Medicines Agency. Published September 17, 2018. [(accessed on 12 December 2021)]. Available online: https://www.ema.europa.eu/en/medicines/human/EPAR/remsima . Hanauer SB, Sands BE, Schreiber S, Danese S, Kłopocka M, Kierkuś J, Kulynych R, Gonciarz M, Sołtysiak A, Smoliński P, Srećković S, Valuyskikh E, Lahat A, Horyński M, Gasbarrini A, Osipenko M, Borzan V, Kowalski M, Saenko D, Sardinov R, Lee SJ, Kim S, Bae Y, Lee S, Lee S, Lee JH, Yang S, Lee J, Lee J, Kim JM, Park G, Sandborn WJ, Colombel JF (2024) Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials (LIBERTY). Gastroenterology 167:919-933. https://doi.org/10.1053/j.gastro.2024.05.006. Buisson A, Nachury M, Reymond M, Yzet C, Wils P, Payen L, Laugie M, Manlay L, Mathieu N, Pereira B, Fumery M (2023) Effectiveness of Switching From Intravenous to Subcutaneous Infliximab in Patients With Inflammatory Bowel Diseases: the REMSWITCH Study. Clin Gastroenterol Hepatol 21:2338-2346.e3. https://doi.org/10.1016/j.cgh.2022.08.011. Roblin X, Veyrard P, Bastide L, Berger AE, Barrau M, Paucelle AS, Waeckel L, Kwiatek S, Flourie B, Nancey S, Paul S (2022) Subcutaneous injection of infliximab CT-P13 results in stable drug levels within 14-day treatment cycle in Crohn's disease. Aliment Pharmacol Ther 56:77-83. https://doi.org/10.1111/apt.16852. Roblin X, Nancey S, Papamichael K, Duru G, Flamand M, Kwiatek S, Cheifetz A, Fabien N, Barrau M, Paul S (2024) Higher Serum Infliximab Concentrations Following Subcutaneous Dosing are Associated with Deep Remission in Patients with Inflammatory Bowel Disease. J Crohns Colitis 18:679-685. https://doi.org/10.1093/ecco-jcc/jjad188. Yarur AJ, Kanagala V, Stein DJ, Czul F, Quintero MA, Agrawal D, Patel A, Best K, Fox C, Idstein K, Abreu MT (2017) Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn's disease. Aliment Pharmacol Ther 45:933-940. https://doi.org/10.1111/apt.13970. Srinivasan A, van Langenberg D, De Cruz P, Segal J, Vasudevan A, Upton RN (2024) Treatment Targets Should Influence Choice of Infliximab Dose Intensification Strategy in Inflammatory Bowel Disease: A Pharmacokinetic Simulation Study. BioDrugs 38:691-702. https://doi.org/10.1007/s40259-024-00673-2. Beek KJ, Mulders LGM, van Rijn KL, Horsthuis K, Tielbeek JAW, Buskens CJ, D'Haens GR, Gecse KB, Stoker J (2025) External validation of the MAGNIFI-CD index in patients with complex perianal fistulising Crohn's disease. Eur Radiol 35:1428-1439. https://doi.org/10.1007/s00330-024-11029-3. Talbot C, Sagar PM, Johnston MJ, Finan PJ, Burke D (2005) Infliximab in the surgical management of complex fistulating anal Crohn's disease. Colorectal Dis 7:164-8. https://doi.org/10.1111/j.1463-1318.2004.00749.x. Bouguen G, Siproudhis L, Gizard E, Wallenhorst T, Billioud V, Bretagne JF, Bigard MA, Peyrin-Biroulet L (2013) Long-term outcome of perianal fistulizing Crohn's disease treated with infliximab. Clin Gastroenterol Hepatol 11:975-81.e1-4. https://doi.org/10.1016/j.cgh.2012.12.042. Haennig A, Staumont G, Lepage B, Faure P, Alric L, Buscail L, Bournet B, Moreau J (2015) The results of seton drainage combined with anti-TNFα therapy for anal fistula in Crohn's disease. Colorectal Dis 17:311-9. https://doi.org/10.1111/codi.12851. Smith PJ, Critchley L, Storey D, Gregg B, Stenson J, Kneebone A, Rimmer T, Burke S, Hussain S, Yi Teoh W, Vazeille S, Serna S, Steel A, Derbyshire E, Collins P, Dibb M, Flanagan P, Probert C, Verma AM, Subramanian S (2022) Efficacy and Safety of Elective Switching from Intravenous to Subcutaneous Infliximab [CT-P13]: A Multicentre Cohort Study. J Crohns Colitis 16:1436-1446. https://doi.org/10.1093/ecco-jcc/jjac053. Huguet JM, García-Lorenzo V, Martí L, Paredes JM, Ramírez JJ, Pastor M, Ruiz L, Sanahuja A, Timoneda P, Sanchís L, Pérez GA, Boscá-Watts MM (2022) Subcutaneous Infliximab [CT-P13], a True Biologic 2.0. Real Clinical Practice Multicentre Study. Biomedicines 10:2130. https://doi.org/10.3390/biomedicines10092130. Bergqvist V, Kadivar M, Molin D, Angelison L, Hammarlund P, Olin M, Torp J, Grip O, Nilson S, Hertervig E, Lillienau J, Marsal J (2018) Switching from originator infliximab to the biosimilar CT-P13 in 313 patients with inflammatory bowel disease. Therap Adv Gastroenterol 11:1756284818801244. https://doi.org/10.1177/1756284818801244. Bronswijk M, Moens A, Lenfant M, Tops S, Compernolle G, Van Assche G, Vermeire S, Gils A, Ferrante M (2020) Evaluating Efficacy, Safety, and Pharmacokinetics After Switching From Infliximab Originator to Biosimilar CT-P13: Experience From a Large Tertiary Referral Center. Inflamm Bowel Dis 26:161. https://doi.org/10.1093/ibd/izz271. Tables Table 1 Description of the study population Description of the study population (n = 39) Median (IQR), n (%) Median age 40 [31.3–46.0] Sex ratio (F/M) 20 F / 19 M Median BMI (kg/m²) 25.1 [21.9–27.7] Active smoking 4 (10.3) Duration of Crohn's disease (years) 4.5 [1.9–15.6] Duration of APL (years) 4.9 [2.1–13.2] Montreal classification - Ileum (L1) 13 (33.3) - Colon (L2) 15 (38.5) - Ileocolonic (L3) 9 (23.1) - Upper gastrointestinal involvement (L4) 2 (5.1) - B1 non-stricturing non-penetrating phenotype 22 (56.4) - B2 stricturing phenotype 5 (12.8) - B3 penetrating phenotype 12 (30.8) Patients with extra-digestive manifestations 17 (43.6) Patients with a history of abdominal surgery 8 (20.5) Patients with a history of proctologic surgery 36 (92.3) Number of proctologic surgeries 3 [1.3–3.0] Patients with a history of proctologic fistula closure surgery 14 (35.9) Patients with a history of anal stricture dilation 1 (2.5) Patients with prior exposure to a biologic therapy 12 (30.8) - Adalimumab 11 - Ustekinumab 1 F: Female ; M: Male Table 2 CT-P13 SC treatment protocols at inclusion Dose of IV Infliximab CT-P13 SC Treatment Protocol Associated Immunosuppressant* (n = 14) CT-P13 SC initiated upfront (n = 17) 5 mg/kg (2/3 infusions) 120 mg every 2 weeks (n = 6) 0 120 mg weekly (n = 11) 7 CT-P13 SC switched from IV (n = 22) 5 mg/kg every 8 weeks (n = 2) 120 mg every 2 weeks (n = 2) 0 10 mg/kg every 8–6–4 weeks (n = 20) 120 mg weekly (n = 9) 5 120 mg every 2 weeks (n = 10) 2 240 mg every 2 weeks (n = 1) 0 *Associated immunosuppressant: mercaptopurine, azathioprine Table 3 Clinical remission data according to CT-P13 SC treatment protocol and disease activity at treatment initiation Clinical data on anoperineal disease at the time of CT-P13 SC initiation CT-P13 SC initiated upfront CT-P13 SC switched from IV Active APL (n = 17) APL in remission (n = 0) APL in complte clinical remission (n = 20) APL in partial clinical remission (n = 2) Clinical data at post-treatment evaluation APL in complete clinical remission (n = 29) 11 0 18 0 APL in partial clinical remission (n = 3) 2 0 1 0 APL with treatment failure (n = 7) 4 0 1 2 Table 4 Deep clinico-radiological remission data according to CT-P13 SC treatment protocols Clinico-radiological remission = no (n = 15) Clinico-radiological remission = yes (n = 24) p-value Protocol according to treatment frequency 0.390 Standard 9 (60.0%) 9 (37.5%) Intensified 6 (40.0%) 15 (62.5%) Protocol according to treatment initiation strategy 0.413 Upfront 9 (60,0%) 8 (33,3%) Switch from IV 6 (40,0%) 16 (66,7%) Table 5 Therapeutic management according to clinical and pharmacokinetic data Treatment persistence with the same frequency Intensification by reducing injection intervals Therapeutic change Upfront SC protocol 120 mg every 2 weeks (n = 6) 4 2 0 120 mg weekly (n = 11) 10 0 1 Switch from IV protocol 120 mg every 2 weeks (n = 12) 10 1 1 120 mg weekly or 240 mg every 2 weeks (n = 10) 8 0 2 Total (n = 39) 32 (82.0%) 3 (7.7%) 4 (10.3%) Additional Declarations Competing interest reported. Nadia Fathallah: received consulting fees from Takeda, lecture fees from Abbvie, Celltrion, Tillots, Janssen, Amgen, Viatris and Sandoz. Vincent de Parades: received consulting fees from Takeda and Abbvie, lectures fees from Amgen, Janssen, Sandoz, Takeda, Tillots. Julien Kirchgesner: received lecture fees from Celltrion, Lilly, and Janssen; consulting fees from Abbvie, Alfasigma, Amgen, Celltrion, Janssen, Takeda, Tillots, and Pfizer. Mohamed Amine Haouari: received lecture fees from Takeda. Edouard Chambenois: received lecture fees from Amgen, Viatris and Mylan. Stéphane Paul : no competing interests. Xavier Roblin : received lecture fees from Celltrion, Lilly, and Janssen ; consulting fees from Abbvie, Alfasigma, Amgen, Celltrion, Janssen, Takeda, Tillots, and Pfizer. Mélanie Draulette : no competing interests. Anne Bourrier : received lecture fees from Ferring and Janssen. Philippe Seksik : received consulting fees from Takeda, Abbvie, Merck-MSD, Biocodex, Janssen, Amgen, Astellas and Pfizer and grants from Biocodex and Janssen. Cite Share Download PDF Status: Published Journal Publication published 25 Jul, 2025 Read the published version in Digestive Diseases and Sciences → Version 1 posted Editorial decision: Revision requested 09 Jun, 2025 Reviews received at journal 09 Jun, 2025 Reviewers agreed at journal 16 Apr, 2025 Reviewers invited by journal 26 Mar, 2025 Editor assigned by journal 25 Mar, 2025 Submission checks completed at journal 20 Mar, 2025 First submitted to journal 19 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-6264439","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":440251541,"identity":"5b5a9f06-7723-461f-b79f-fccf654ca496","order_by":0,"name":"Nadia 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20:53:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6264439/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6264439/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10620-025-09210-9","type":"published","date":"2025-07-25T15:57:46+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80707846,"identity":"89e2fb12-d853-4c35-aefe-044e90534867","added_by":"auto","created_at":"2025-04-16 08:49:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":63308,"visible":true,"origin":"","legend":"\u003cp\u003eFlow Chart\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6264439/v1/feab5277ee8506b48b480313.png"},{"id":80709873,"identity":"0a332944-f66b-4898-95cf-1d8932e2747b","added_by":"auto","created_at":"2025-04-16 08:57:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":63022,"visible":true,"origin":"","legend":"\u003cp\u003eAnoperineal clinical remission rate under CT-P13 SC\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6264439/v1/dd80d0767ef02c50d17725f8.png"},{"id":80707849,"identity":"b67a9313-eb21-407e-b0e5-c23a5eeba3ae","added_by":"auto","created_at":"2025-04-16 08:49:30","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":44804,"visible":true,"origin":"","legend":"\u003cp\u003eAnoperineal clinico-radiological remission rate under CT-P13 SC\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6264439/v1/ff495f8ac95937406837431e.png"},{"id":80711064,"identity":"cd29a727-9b86-4c06-b87a-b4adbff42296","added_by":"auto","created_at":"2025-04-16 09:05:30","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":19154,"visible":true,"origin":"","legend":"\u003cp\u003eProbability of survival without therapeutic change in patients with Crohn's disease-related APL treated with CT-P13 SC\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6264439/v1/2d384e7477e213579abb9a69.png"},{"id":88506144,"identity":"717e56ab-40ee-4b94-93cc-bd4eb20bf20e","added_by":"auto","created_at":"2025-08-07 07:31:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1243298,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6264439/v1/3f210c33-0207-4411-8e52-1849ca44da54.pdf"}],"financialInterests":"Competing interest reported. Nadia Fathallah: received consulting fees from Takeda, lecture fees from Abbvie, Celltrion, Tillots, Janssen, Amgen, Viatris and Sandoz.\nVincent de Parades: received consulting fees from Takeda and Abbvie, lectures fees from Amgen, Janssen, Sandoz, Takeda, Tillots.\nJulien Kirchgesner: received lecture fees from Celltrion, Lilly, and Janssen; consulting fees from Abbvie, Alfasigma, Amgen, Celltrion, Janssen, Takeda, Tillots, and Pfizer.\nMohamed Amine Haouari: received lecture fees from Takeda.\nEdouard Chambenois: received lecture fees from Amgen, Viatris and Mylan.\nStéphane Paul : no competing interests.\nXavier Roblin : received lecture fees from Celltrion, Lilly, and Janssen ; consulting fees from Abbvie, Alfasigma, Amgen, Celltrion, Janssen, Takeda, Tillots, and Pfizer.\nMélanie Draulette : no competing interests.\nAnne Bourrier : received lecture fees from Ferring and Janssen.\nPhilippe Seksik : received consulting fees from Takeda, Abbvie, Merck-MSD, Biocodex, Janssen, Amgen, Astellas and Pfizer and grants from Biocodex and Janssen.","formattedTitle":"Clinical, Radiological and Pharmacokinetic Data of CT-P13 Subcutaneous in Fistulizing Anoperineal Lesions of Crohn’s Disease","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe recommendations of the European Crohn\u0026apos;s and Colitis Organisation (ECCO) [1] and the French National Society of Coloproctology (SNFCP) [2] indicate infliximab as the first-line treatment for perianal lesions (PAL) in Crohn\u0026apos;s disease, following the work of Present et al. and the ACCENT II study [3-4]. A subcutaneous formulation of infliximab (CT-P13 SC) has been developed for maintenance therapy, offering the possibility of self-administration [5-6]. In 2020, this formulation received regulatory approval from the European Medicines Agency (EMA) for all previously approved indications of intravenous (IV) infliximab, including inflammatory bowel diseases [7].\u003c/p\u003e\n\u003cp\u003eThe phase 3 randomized controlled trial Liberty demonstrated the efficacy of CT-P13 SC versus placebo specifically in luminal Crohn\u0026rsquo;s disease. After 56 weeks of follow-up, the rate of complete clinical remission was 62.3% compared to 32.1% (p \u0026lt; 0.0001), and the rate of endoscopic response was 51.1% compared to 17.9% (p \u0026lt; 0.0001). The safety profile was also favorable [8]. In another randomized controlled non-inferiority trial, pharmacokinetic data, efficacy, safety, and immunogenicity appeared similar between the IV and SC formulations [6]. In the Remswitch study, switching from IV to SC infliximab at 120 mg every 2 weeks maintained luminal remission in the vast majority of patients; only those previously receiving infliximab IV at 10 mg/kg every 4 weeks required therapeutic intensification to 240 mg every 2 weeks [9].\u003c/p\u003e\n\u003cp\u003eRegarding pharmacokinetic monitoring, unlike IV infliximab, the concentration of the SC formulation appears to remain stable between injections, allowing for simplified monitoring that can be performed at any time between doses [10]. Additionally, similar to residual levels of IV infliximab, high serum infliximab concentrations (\u0026gt; 20 \u0026micro;g/ml) with the SC formulation were associated with higher rates of long-term clinical remission, with a sensitivity of 0.91, specificity of 0.80, and accuracy of 0.85. Finally, concomitant immunosuppressive therapy did not appear to impact pharmacokinetic measurements [11].\u003c/p\u003e\n\u003cp\u003eIn the specific case of\u0026nbsp;PAL, high residual serum levels of intravenous infliximab (\u0026gt;10.10 mg/L), or even above 20 mg/L, also appear to be preferable in terms of efficacy [12]. Patients are often treated with intensified protocols of 10 mg/kg every 6 weeks, or even every 4 weeks [13].\u003c/p\u003e\n\u003cp\u003eTo date, there is no specific publication regarding the use of CT-P13 SC in Crohn\u0026rsquo;s disease PAL. Therefore, the aim of our study was to assess its efficacy in the treatment of fistulizing PAL and its correlation with pharmacokinetic data.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design and Data Collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe included all consecutive patients over 18 years of age who were seen in a dedicated medical-surgical proctology outpatient clinic between June 1st and July 15th, 2024, in two French centers (Saint-Joseph Hospital and Saint-Antoine Hospital in Paris). Eligible patients had been treated with CT-P13 SC for at least 3 months and presented with fistulizing PAL associated with Crohn\u0026rsquo;s disease. The 3-month treatment duration criterion was established in order to reach a minimum sample size of 30 patients. During this period, patients who had previously received CT-P13 but discontinued it due to treatment failure were also documented.\u003c/p\u003e\n\u003cp\u003eWe collected demographic data, including age, sex, weight, smoking status, disease extent and phenotype, history of proctologic interventions, Harvey-Bradshaw Index score, fecal calprotectin levels, and data on luminal remission as assessed by the most recent colonoscopy performed prior to the consultation.\u003c/p\u003e\n\u003cp\u003eThe CT-P13 SC treatment regimen was categorized as follows:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003estandard\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003e120 mg every 2 weeks\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eintensified\u003c/strong\u003e: 120 mg weekly or 240 mg every 2 weeks\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe initiation scheme was also differentiated as:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003einitiated upfront :\u0026nbsp;\u003cstrong\u003eimmediately after\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e2 or 3 standard IV infusions (Week 0, Week 2, Week 6)\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ea switch\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003efrom a previous IV maintenance phase\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe dose, frequency, and duration of prior IV infliximab treatment were specified.\u003c/p\u003e\n\u003cp\u003eThe clinical status of perianal disease at the time of CT-P13 SC initiation was recorded (remission/active disease). It is important to note that no patients with complete failure of IV infliximab therapy were transitioned to CT-P13 SC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinition of Evaluation Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe clinical proctological evaluation of the anoperineal area was performed by a specialized surgical proctologist on the day of inclusion in each of the two centers. Clinical outcomes were defined as follows:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eComplete clinical remission corresponded to the closure of all external fistula openings, without pain, discharge under pressure, or abscesses.\u003c/li\u003e\n \u003cli\u003eClinical response corresponded to partial closure of the external fistula openings and/or a decrease in pain and discharge under pressure, without abscesses.\u003c/li\u003e\n \u003cli\u003eTreatment failure corresponded to the absence of a clinical response and/or the development of a new abscess and/or fistula.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe PDAI score was also calculated for all patients.\u003c/p\u003e\n\u003cp\u003eRadiological assessment was based on data from an anoperineal MRI performed at least 3 months after the initiation of CT-P13 SC therapy. All MRIs were reviewed by a radiologist specialized in APL related to Crohn\u0026rsquo;s disease in each of the two centers. The Magnifi-CD score was calculated. Radiological remission was defined as a Magnifi-CD score \u0026lt; 6 [14]. Deep combined clinico-radiological remission was defined as the association of complete clinical remission with radiological remission.\u003cbr\u003e\u0026nbsp;On the day of the consultation, patients underwent blood sampling for pharmacokinetic tests (serum infliximab levels and anti-infliximab antibodies testing), as well as fecal calprotectin measurement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePharmacokinetic Sampling Technique\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInfliximab serum levels were measured using an automated enzyme-linked immunosorbent assay (ELISA) (i-Track10, Theradiag, Marne La Vall\u0026eacute;e, France) as per the manufacturer\u0026rsquo;s instructions. The samples were diluted with the kit assay buffer at either 1:20, 1:10 or 1:4 as required, and the concentration was determined from the standard curve multiplied by the dilution factor. The upper limit of the assay was 24 \u0026mu;g/ml and the lower limit of quantification was 0,3 \u0026mu;g/ml. Given the assay used in our institution is drug-sensitive, Assessment for anti-drug antibodies was only performed on samples with a drug level \u0026lt; 0,5 \u0026mu;g/ml.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTherapeutic Management Based on Clinico-Radiological and Pharmacokinetic Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were contacted 3 months after the inclusion visit to determine the subsequent therapeutic management, taking into account clinico-radiological and pharmacokinetic data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Objectives\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary endpoint was the rate of deep clinico-radiological remission of fistulizing APL under CT-P13 SC at the inclusion visit.\u003c/p\u003e\n\u003cp\u003eSecondary endpoints were:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eLuminal disease data\u003c/li\u003e\n \u003cli\u003ePharmacokinetic data and their association with deep clinico-radiological remission\u003c/li\u003e\n \u003cli\u003eThe persistence rate of CT-P13 SC treatment from initiation until the 3-month follow-up visit\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eEthics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the ethics committee of Saint-Joseph Hospital (IRB 00012157), and all patients signed an information and non-opposition form for the collection of their data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study was partially funded by Celltrion Laboratories to cover the costs of pharmacokinetic assays, which are not reimbursed by the French national health insurance system. The study\u0026rsquo;s primary sponsor was Saint-Joseph Hospital, which was responsible for data centralization and statistical analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using R software (v4.3.2). Continuous variables were expressed as median and interquartile range [IQR] or as mean \u0026plusmn; standard deviation, according to their distribution assessed by the Shapiro-Wilk test. Comparisons between groups were performed using the Mann-Whitney test for non-parametric continuous variables and Student\u0026rsquo;s t-test for normally distributed variables. Categorical variables were compared using the chi-square test or Fisher\u0026rsquo;s exact test when expected counts were less than 5.\u003c/p\u003e\n\u003cp\u003eThe association between serum infliximab levels and deep clinico-radiological remission was assessed using Spearman\u0026rsquo;s correlation analysis. Univariate and multivariate logistic regression analyses were performed to identify predictors of deep clinico-radiological remission, adjusting for relevant variables (age, surgical history, SC initiation versus IV switch, infliximab serum levels, etc.). Results were reported as odds ratios (OR) with their 95% confidence intervals (95% CI).\u003c/p\u003e\n\u003cp\u003eTreatment persistence was assessed using Kaplan-Meier survival analysis, with survival curves compared by the log-rank test. A p-value \u0026lt; 0.05 was considered statistically significant for all analyses.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eStudy Population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the study period, 43 patients with fistulizing APL associated with Crohn\u0026rsquo;s disease were treated with CT-P13 SC. Three patients were not included because they had received less than 3 months of treatment. During the study period, no patients seen in consultation had previously been treated with CT-P13 SC and discontinued due to treatment failure.\u003cbr\u003e\u0026nbsp;In total, 40 patients were included in the study. However, one patient was excluded from the analysis because she was in early pregnancy at the time of sampling (Figure 1).\u003cbr\u003e\u0026nbsp;Fistulizing APL was complex in 38 patients, including 2 cases of rectovaginal fistulas. Three patients had associated ulcerated anal involvement, and four patients had associated stenosing disease.\u003c/p\u003e\n\u003cp\u003eTable 1 describes the study population.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDescription of CT-P13 SC Treatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCT-P13 SC treatment was prescribed as follows:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eInitiated upfront in 17 patients\u003c/li\u003e\n \u003cli\u003eAs a switch from IV infliximab in 22 patients, with a median time between the switch from IV to SC of 61.6 months [22.4\u0026ndash;142.4].\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAll patients who received CT-P13 SC as an upfront treatment had active APL. In this group, during follow-up, 11 patients initially treated with standard doses of CT-P13 SC required intensification to 120 mg weekly due to partial clinical response of the APL.\u003cbr\u003e\u0026nbsp;Among the patients who switched from IV to CT-P13 SC, 20 were in complete remission and 2 in partial response. Of those who were on intensified IV maintenance therapy, 50% were immediately transitioned to intensified CT-P13 SC protocols.\u003cbr\u003e\u0026nbsp;Table 2 details the treatment protocols at the time of the inclusion visit.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeep Clinico-Radiological Remission Rate of APL\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt the time of evaluation, after a median duration of CT-P13 SC treatment of 16.1 months [10.3\u0026ndash;25.7], 29 patients (74.4%) were in complete clinical remission, 3 patients (7.7%) were in partial remission, and 7 patients (17.9%) were considered treatment failures (Table 3) (Figure 2).\u003cbr\u003e\u0026nbsp;The complete clinical remission rate was 64.7% in patients who initiated SC treatment upfront and 81.8% in those who switched from IV therapy (OR [95% CI] = 4.3 [1.1\u0026ndash;17.9], p = 0.042), with no statistically significant difference in treatment exposure duration: 12.7 months (6.0; 36.7) [9.0\u0026ndash;25.1] versus 19.5 [14.0\u0026ndash;23.3] (p = 0.203) (Table 3).\u003cbr\u003e\u0026nbsp;The median PDAI score was 0.5 [0\u0026ndash;4].\u003cbr\u003e\u0026nbsp;Finally, the median Magnifi-CD score was 0 [0\u0026ndash;10], and 24 patients had a Magnifi-CD score \u0026lt; 6.\u003c/p\u003e\n\u003cp\u003eThe deep clinico-radiological remission rate was therefore 61.5% (Figure 3). It is reported according to the administration protocol in Table 4.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLuminal Disease Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median Harvey-Bradshaw Index score was 1 [0\u0026ndash;4], with no significant difference between patients with or without deep anoperineal clinico-radiological remission (1 [0.0\u0026ndash;3.3] versus 2 [0.5\u0026ndash;5.0], p = 0.418).\u003c/p\u003e\n\u003cp\u003eTwenty-three patients (59.0%) were in complete luminal remission: 16 patients (66.7%) in the group with deep anoperineal clinico-radiological remission versus 7 patients (46.7%) in the group without remission (p = 0.157).\u003c/p\u003e\n\u003cp\u003eThe median fecal calprotectin level was 79.2 \u0026micro;g/g [35.5\u0026ndash;133.0], with no difference between patients with or without deep anoperineal clinico-radiological remission (79.2 \u0026micro;g/g [50.0\u0026ndash;116.0] versus 80.0 \u0026micro;g/g [45.0\u0026ndash;115.0]).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePharmacokinetic Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median infliximab concentration was 22.7 \u0026micro;g/ml [19.3\u0026ndash;38.6]. It was \u0026lt; 23 \u0026micro;g/ml in 20 patients and \u0026ge; 24 \u0026micro;g/ml in 19 patients. Among patients with infliximab concentrations \u0026ge; 24 \u0026micro;g/ml, the median was 40 \u0026micro;g/ml [36.9\u0026ndash;46.5], and one patient reached a concentration of 80.8 \u0026micro;g/ml.\u003c/p\u003e\n\u003cp\u003eAnti-infliximab antibodies associated with an infliximab concentration \u0026lt; 0.3 \u0026micro;g/ml were detected in 2 patients. One of these 2 patients had previously received IV therapy before switching to SC and did not have antibodies at that time.\u003c/p\u003e\n\u003cp\u003eThe intensified CT-P13 SC administration protocol was significantly associated with a higher infliximab concentration (OR = 16.7 [27.4\u0026ndash;6.0], p = 0.004).\u003c/p\u003e\n\u003cp\u003eThe use of concomitant immunosuppressive therapy, demographic data, and the administration protocol (upfront SC versus switch from IV) were not associated with infliximab concentration levels.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation Between Pharmacokinetic Data and Deep Clinico-Radiological Remission\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median infliximab concentration was 35.9 \u0026micro;g/ml [20.2\u0026ndash;41.5] in patients in remission versus 22.4 \u0026micro;g/ml [16.5\u0026ndash;36] in patients without remission, but the difference was not statistically significant (p = 0.184).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment Persistence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTherapeutic management of patients, based on clinical, radiological response and pharmacokinetic data, is summarized in Table 5.\u003c/p\u003e\n\u003cp\u003eA change in therapy was considered in 4 out of 7 patients with clinical failure:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e2 patients had a partial response to IV infliximab and subsequently failed intensified CT-P13 SC (infliximab concentration \u0026gt; 24 \u0026micro;g/ml without antibodies);\u003c/li\u003e\n \u003cli\u003e1 patient was in complete remission with IV therapy and became active after switching to SC, with an infliximab concentration \u0026lt; 0.3 \u0026micro;g/ml and anti-infliximab antibodies at 243 \u0026micro;g/ml;\u003c/li\u003e\n \u003cli\u003e1 patient from the CT-P13 SC upfront group did not respond to intensification (infliximab concentration \u0026gt; 24 \u0026micro;g/ml without antibodies).\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eTherapeutic intensification was considered in 3 patients:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e2 patients with treatment failure in the CT-P13 SC upfront group (infliximab concentration \u0026lt; 24 \u0026micro;g/ml without antibodies);\u003c/li\u003e\n \u003cli\u003e1 patient with partial response in the CT-P13 SC upfront group (infliximab concentration \u0026lt; 0.3 \u0026micro;g/ml with antibodies at 28 \u0026micro;g/ml). Azathioprine was also added to the treatment regimen.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe treatment was not modified in 3 patients, at their request despite the absence of remission:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e1 patient with failure of CT-P13 SC initiated upfront with the standard protocol, infliximab concentration at 22.7 \u0026micro;g/ml without antibodies;\u003c/li\u003e\n \u003cli\u003e2 patients with partial response (1 in the CT-P13 SC upfront group and 1 switched from IV therapy), both under the standard protocol with infliximab concentration \u0026gt; 24 \u0026micro;g/ml.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eIn the end, after a median duration of 16.1 months [10.3\u0026ndash;25.7] of CT-P13 SC treatment, 24 patients (61.5%) were receiving an intensified dose. This protocol had been initiated from the start in 10 patients who had switched from intensified IV therapy and was subsequently adjusted according to the clinico-radiological response \u0026plusmn; pharmacokinetic data in the other patients (11 before the inclusion visit and 3 afterwards).\u003c/p\u003e\n\u003cp\u003eCT-P13 SC treatment was discontinued in 4 out of 39 patients (10.3%). Among patients who switched from IV to SC, 86.4% maintained their treatment.\u003c/p\u003e\n\u003cp\u003eFigure 4 shows the probability of survival without therapeutic change in patients with APL treated with CT-P13 SC.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe conducted the first prospective, bicentric study assessing the clinico-radiological response and its correlation with pharmacokinetic data in patients with fistulizing APL treated with CT-P13 SC. More than two-thirds of patients were receiving infliximab as first-line therapy. After a median exposure of 16 months to CT-P13 SC, the deep clinico-radiological remission rate was 61.5%. In addition, the complete clinical remission rate was 74.4%.\u003c/p\u003e\n\u003cp\u003eIf we consider the pivotal studies on IV infliximab [3-4], the efficacy of the SC formulation appears to be superior. However, in real-life settings, the efficacy of IV infliximab combined with surgical treatment of APL varies from 47% to 88%, which is more consistent with our findings [15-17].\u003c/p\u003e\n\u003cp\u003eThe recurrence rate after switching from IV to SC formulation was low in our cohort and consistent with data from the literature. Among patients who switched from IV to SC, 86.4% were able to continue treatment. Only one patient experienced disease progression after having been in remission under IV therapy, while the two other patients already had a partial response on IV infliximab.\u003c/p\u003e\n\u003cp\u003eThe overall CT-P13 SC treatment persistence rate, considering both protocols (upfront initiation/switch from IV), was excellent at 89.7%. In a series of 181 patients with inflammatory bowel disease treated with CT-P13 SC, 2 out of 25 patients with Crohn\u0026rsquo;s disease-related APL experienced recurrence [18]. In another series including only 9 patients with APL, none showed disease progression [19].\u003c/p\u003e\n\u003cp\u003eIn our cohort, patients initially treated with IV infliximab before switching to the SC formulation achieved higher rates of clinical remission compared to those who received SC treatment upfront. However, this difference disappeared when considering deep clinico-radiological remission, although the numerical rates remained higher (66.7% after IV switch versus 33.3% with upfront SC treatment), likely due to limited statistical power.\u003c/p\u003e\n\u003cp\u003eIt is important to note that the vast majority of patients had severe APL and that 90.9% were receiving intensified IV infliximab protocols prior to switching. Moreover, no data from the existing literature currently support such a treatment sequence in APL.\u003c/p\u003e\n\u003cp\u003eRegarding pharmacokinetic data, Roblin et al. demonstrated that a cut-off infliximab concentration of 20 \u0026micro;g/ml was necessary to achieve deep luminal remission [11]. It is also well known that APL requires high residual IV infliximab levels [12]. In our cohort, the median infliximab concentration was elevated at 22.7 \u0026micro;g/ml [19.3\u0026ndash;38.6], and it was \u0026ge; 24 \u0026micro;g/ml in 48.7% of patients. Neutralizing anti-infliximab antibodies were detected in only 5.1% of patients, consistent with previously reported low rates [20-21].\u003c/p\u003e\n\u003cp\u003eImmunosuppressants did not appear to impact the pharmacokinetics of the SC formulation, in contrast to what has been observed with IV infliximab [20-21]. However, although infliximab concentrations were higher in patients achieving deep clinico-radiological remission compared to those who did not, there was no statistically significant difference in our series\u0026mdash;likely due to limited statistical power and the large proportion of patients (53.8%) already on intensified SC protocols.\u003c/p\u003e\n\u003cp\u003eOur study has two main limitations: the limited number of patients, which is explained by the high cost of pharmacokinetic testing, and the absence of long-term follow-up under treatment., et l\u0026rsquo;absence de suivi prolong\u0026eacute; sous traitement.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study in patients treated with CT-P13 SC for complex fistulizing APL demonstrated a deep clinico-radiological remission rate of 61.5%, with an intensified treatment protocol in more than half of the cases. There was no significant correlation between pharmacokinetic data and deep remission, although infliximab concentrations were higher in patients in remission.\u003c/p\u003e\n\u003cp\u003eInterestingly, patients initially treated with IV infliximab and subsequently switched to SC therapy appeared more likely to achieve complete clinical remission.\u003c/p\u003e\n\u003cp\u003eFinally, the treatment persistence rate was 89.7%, and only 13.6% of patients experienced disease progression after switching from IV to SC. These preliminary results are promising but will, of course, need to be confirmed by further studies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT-P13 SC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esubcutaneous infliximab\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePAL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePerianal lesions\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintravenous\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esubcutaneous\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDisclosures and declarations: Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNadia Fathallah: received\u0026nbsp;consulting fees from Takeda, lecture fees from Abbvie, Celltrion, Tillots, Janssen, Amgen, Viatris and Sandoz.\u003c/p\u003e\n\u003cp\u003eVincent de Parades: received\u0026nbsp;consulting fees from Takeda and Abbvie, lectures fees from Amgen, Janssen, Sandoz, Takeda, Tillots.\u003c/p\u003e\n\u003cp\u003eJulien Kirchgesner:\u0026nbsp;received\u0026nbsp;lecture fees from Celltrion, Lilly, and Janssen; consulting fees from Abbvie, Alfasigma, Amgen, Celltrion, Janssen, Takeda, Tillots, and Pfizer.\u003c/p\u003e\n\u003cp\u003eMohamed Amine Haouari: received\u0026nbsp;lecture fees from Takeda.\u003c/p\u003e\n\u003cp\u003eEdouard Chambenois: received\u0026nbsp;lecture fees from\u0026nbsp;Amgen, Viatris and Mylan.\u003c/p\u003e\n\u003cp\u003eSt\u0026eacute;phane Paul : no competing interests.\u003c/p\u003e\n\u003cp\u003eXavier Roblin : received\u0026nbsp;lecture fees from Celltrion, Lilly, and Janssen ; consulting fees from Abbvie, Alfasigma, Amgen, Celltrion, Janssen, Takeda, Tillots, and Pfizer.\u003c/p\u003e\n\u003cp\u003eM\u0026eacute;lanie Draulette : no competing interests.\u003c/p\u003e\n\u003cp\u003eAnne Bourrier : received lecture fees from Ferring and Janssen\u003c/p\u003e\n\u003cp\u003ePhilippe Seksik : received consulting fees from Takeda, Abbvie, Merck-MSD, Biocodex, Janssen, Amgen, Astellas and Pfizer and grants from Biocodex and Janssen.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAknowledgment:\u003c/strong\u003e We would like to thank the clinical research centers of Saint-Joseph and Saint-Antoine for their help in carrying out this project\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Transparency:\u003c/strong\u003e Data are valid upon online request on a secure REDCAP site\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration number and date\u0026nbsp;:\u003c/strong\u003e Registration with the ethics committee on 11/14/2023.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTorres J, Bonovas S, Doherty G, Kucharzik T, Gisbert JP, Raine T, Adamina M, Armuzzi A, Bachmann O, Bager P, Biancone L, Bokemeyer B, Bossuyt P, Burisch J, Collins P, El-Hussuna A, Ellul P, Frei-Lanter C, Furfaro F, Gingert C, Gionchetti P, Gomollon F, Gonz\u0026aacute;lez-Lorenzo M, Gordon H, Hlavaty T, Juillerat P, Katsanos K, Kopylov U, Krustins E, Lytras T, Maaser C, Magro F, Marshall JK, Myrelid P, Pellino G, Rosa I, Sabino J, Savarino E, Spinelli A, Stassen L, Uzzan M, Vavricka S, Verstockt B, Warusavitarne J, Zmora O, Fiorino G (2020) ECCO Guidelines on Therapeutics in Crohn\u0026apos;s Disease: Medical Treatment. J Crohns Colitis 14 :4-22. https://doi.org/10.1093/ecco-jcc/jjz180.\u003c/li\u003e\n\u003cli\u003eBouchard D, Pigot F, Staumont G, Siproudhis L, Abramowitz L, Benfredj P, Brochard C, Fathallah N, Faucheron JL, Higuero T, Panis Y, de Parades V, Vinson-Bonnet B, Laharie D (2018) Management of anoperineal lesions in Crohn\u0026apos;s disease: a French National Society of Coloproctology national consensus. Tech Coloproctol 22:905-917. https://doi.org/10.1007/s10151-018-1906-y.\u003c/li\u003e\n\u003cli\u003ePresent DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, Podolsky DK, Sands BE, Braakman T, DeWoody KL, Schaible TF, van Deventer SJ (1999) Infliximab for the treatment of fistulas in patients with Crohn\u0026apos;s disease. N Engl J Med 340:1398-405. https://doi.org/10.1056/NEJM199905063401804. \u003c/li\u003e\n\u003cli\u003eSands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ (2004) Infliximab maintenance therapy for fistulizing Crohn\u0026apos;s disease. N Engl 350:876-85. https://doi.org/10.1056/NEJMoa030815.\u003c/li\u003e\n\u003cli\u003eParigi TL, D\u0026apos;Amico F, Peyrin-Biroulet L, Danese S. Evolution of infliximab biosimilar in inflammatory bowel disease: from intravenous to subcutaneous CT-P13 (2021) Expert Opin Biol Ther 21:37-46. https://doi.org/10.1080/14712598.2020.1811849.\u003c/li\u003e\n\u003cli\u003eSchreiber S, Ben-Horin S, Leszczyszyn J, Dudkowiak R, Lahat A, Gawdis-Wojnarska B, Pukitis A, Horynski M, Farkas K, Kierkus J, Kowalski M, Lee SJ, Kim SH, Suh JH, Kim MR, Lee SG, Ye BD, Reinisch W (2021) Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease. Gastroenterology 160:2340-2353. https://doi.org/10.1053/j.gastro.2021.02.068. \u003c/li\u003e\n\u003cli\u003e\u003ccite\u003eEuropean Medicines Agency Remsima. European Medicines Agency. Published September 17, 2018. [(accessed on 12 December 2021)]. Available online: \u003c/cite\u003e\u003cem\u003ehttps://www.ema.europa.eu/en/medicines/human/EPAR/remsima\u003c/em\u003e\u003ccite\u003e.\u003c/cite\u003e\u003c/li\u003e\n\u003cli\u003eHanauer SB, Sands BE, Schreiber S, Danese S, Kłopocka M, Kierkuś J, Kulynych R, Gonciarz M, Sołtysiak A, Smoliński P, Srećković S, Valuyskikh E, Lahat A, Horyński M, Gasbarrini A, Osipenko M, Borzan V, Kowalski M, Saenko D, Sardinov R, Lee SJ, Kim S, Bae Y, Lee S, Lee S, Lee JH, Yang S, Lee J, Lee J, Kim JM, Park G, Sandborn WJ, Colombel JF (2024) Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials (LIBERTY). Gastroenterology 167:919-933. https://doi.org/10.1053/j.gastro.2024.05.006. \u003c/li\u003e\n\u003cli\u003eBuisson A, Nachury M, Reymond M, Yzet C, Wils P, Payen L, Laugie M, Manlay L, Mathieu N, Pereira B, Fumery M (2023) Effectiveness of Switching From Intravenous to Subcutaneous Infliximab in Patients With Inflammatory Bowel Diseases: the REMSWITCH Study. Clin Gastroenterol Hepatol 21:2338-2346.e3. https://doi.org/10.1016/j.cgh.2022.08.011.\u003c/li\u003e\n\u003cli\u003eRoblin X, Veyrard P, Bastide L, Berger AE, Barrau M, Paucelle AS, Waeckel L, Kwiatek S, Flourie B, Nancey S, Paul S (2022) Subcutaneous injection of infliximab CT-P13 results in stable drug levels within 14-day treatment cycle in Crohn\u0026apos;s disease. Aliment Pharmacol Ther 56:77-83. https://doi.org/10.1111/apt.16852.\u003c/li\u003e\n\u003cli\u003eRoblin X, Nancey S, Papamichael K, Duru G, Flamand M, Kwiatek S, Cheifetz A, Fabien N, Barrau M, Paul S (2024) Higher Serum Infliximab Concentrations Following Subcutaneous Dosing are Associated with Deep Remission in Patients with Inflammatory Bowel Disease. J Crohns Colitis 18:679-685. https://doi.org/10.1093/ecco-jcc/jjad188.\u003c/li\u003e\n\u003cli\u003eYarur AJ, Kanagala V, Stein DJ, Czul F, Quintero MA, Agrawal D, Patel A, Best K, Fox C, Idstein K, Abreu MT (2017) Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn\u0026apos;s disease. Aliment Pharmacol Ther 45:933-940. https://doi.org/10.1111/apt.13970.\u003c/li\u003e\n\u003cli\u003eSrinivasan A, van Langenberg D, De Cruz P, Segal J, Vasudevan A, Upton RN (2024) Treatment Targets Should Influence Choice of Infliximab Dose Intensification Strategy in Inflammatory Bowel Disease: A Pharmacokinetic Simulation Study. BioDrugs 38:691-702. https://doi.org/10.1007/s40259-024-00673-2.\u003c/li\u003e\n\u003cli\u003eBeek KJ, Mulders LGM, van Rijn KL, Horsthuis K, Tielbeek JAW, Buskens CJ, D\u0026apos;Haens GR, Gecse KB, Stoker J (2025) External validation of the MAGNIFI-CD index in patients with complex perianal fistulising Crohn\u0026apos;s disease. Eur Radiol 35:1428-1439. https://doi.org/10.1007/s00330-024-11029-3.\u003c/li\u003e\n\u003cli\u003eTalbot C, Sagar PM, Johnston MJ, Finan PJ, Burke D (2005) Infliximab in the surgical management of complex fistulating anal Crohn\u0026apos;s disease. Colorectal Dis 7:164-8. https://doi.org/10.1111/j.1463-1318.2004.00749.x.\u003c/li\u003e\n\u003cli\u003eBouguen G, Siproudhis L, Gizard E, Wallenhorst T, Billioud V, Bretagne JF, Bigard MA, Peyrin-Biroulet L (2013) Long-term outcome of perianal fistulizing Crohn\u0026apos;s disease treated with infliximab. Clin Gastroenterol Hepatol 11:975-81.e1-4. https://doi.org/10.1016/j.cgh.2012.12.042.\u003c/li\u003e\n\u003cli\u003eHaennig A, Staumont G, Lepage B, Faure P, Alric L, Buscail L, Bournet B, Moreau J (2015) The results of seton drainage combined with anti-TNF\u0026alpha; therapy for anal fistula in Crohn\u0026apos;s disease. Colorectal Dis 17:311-9. https://doi.org/10.1111/codi.12851. \u003c/li\u003e\n\u003cli\u003eSmith PJ, Critchley L, Storey D, Gregg B, Stenson J, Kneebone A, Rimmer T, Burke S, Hussain S, Yi Teoh W, Vazeille S, Serna S, Steel A, Derbyshire E, Collins P, Dibb M, Flanagan P, Probert C, Verma AM, Subramanian S (2022) Efficacy and Safety of Elective Switching from Intravenous to Subcutaneous Infliximab [CT-P13]: A Multicentre Cohort Study. J Crohns Colitis 16:1436-1446. https://doi.org/10.1093/ecco-jcc/jjac053. \u003c/li\u003e\n\u003cli\u003eHuguet JM, Garc\u0026iacute;a-Lorenzo V, Mart\u0026iacute; L, Paredes JM, Ram\u0026iacute;rez JJ, Pastor M, Ruiz L, Sanahuja A, Timoneda P, Sanch\u0026iacute;s L, P\u0026eacute;rez GA, Bosc\u0026aacute;-Watts MM (2022) Subcutaneous Infliximab [CT-P13], a True Biologic 2.0. Real Clinical Practice Multicentre Study. Biomedicines 10:2130. https://doi.org/10.3390/biomedicines10092130.\u003c/li\u003e\n\u003cli\u003eBergqvist V, Kadivar M, Molin D, Angelison L, Hammarlund P, Olin M, Torp J, Grip O, Nilson S, Hertervig E, Lillienau J, Marsal J (2018) Switching from originator infliximab to the biosimilar CT-P13 in 313 patients with inflammatory bowel disease. Therap Adv Gastroenterol 11:1756284818801244. https://doi.org/10.1177/1756284818801244.\u003c/li\u003e\n\u003cli\u003eBronswijk M, Moens A, Lenfant M, Tops S, Compernolle G, Van Assche G, Vermeire S, Gils A, Ferrante M (2020) Evaluating Efficacy, Safety, and Pharmacokinetics After Switching From Infliximab Originator to Biosimilar CT-P13: Experience From a Large Tertiary Referral Center. Inflamm Bowel Dis 26:161. https://doi.org/10.1093/ibd/izz271. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":" \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 \u003cdiv class=\"SimplePara\"\u003eDescription of the study population\u003c/div\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 \u003cdiv class=\"SimplePara\"\u003eDescription of the study population (n\u0026thinsp;=\u0026thinsp;39)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eMedian (IQR), n (%)\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMedian age\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e40 [31.3\u0026ndash;46.0]\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eSex ratio (F/M)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e20 F / 19 M\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMedian BMI (kg/m\u0026sup2;)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e25.1 [21.9\u0026ndash;27.7]\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eActive smoking\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (10.3)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eDuration of Crohn's disease (years)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4.5 [1.9\u0026ndash;15.6]\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eDuration of APL (years)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4.9 [2.1\u0026ndash;13.2]\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMontreal classification\u003c/div\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 \u003cdiv class=\"SimplePara\"\u003e- Ileum (L1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e13 (33.3)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e- Colon (L2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e15 (38.5)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e- Ileocolonic (L3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e9 (23.1)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e- Upper gastrointestinal involvement (L4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (5.1)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e- B1 non-stricturing non-penetrating phenotype\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e22 (56.4)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e- B2 stricturing phenotype\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 (12.8)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e- B3 penetrating phenotype\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e12 (30.8)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePatients with extra-digestive manifestations\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e17 (43.6)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePatients with a history of abdominal surgery\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e8 (20.5)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePatients with a history of proctologic surgery\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e36 (92.3)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNumber of proctologic surgeries\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 [1.3\u0026ndash;3.0]\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePatients with a history of proctologic fistula closure surgery\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e14 (35.9)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePatients with a history of anal stricture dilation\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (2.5)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePatients with prior exposure to a biologic therapy\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e12 (30.8)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e- Adalimumab\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e11\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e- Ustekinumab\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eF: Female ; M: Male\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\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 \u003cdiv class=\"SimplePara\"\u003eCT-P13 SC treatment protocols at inclusion\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eDose of IV Infliximab\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCT-P13 SC Treatment Protocol\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eAssociated Immunosuppressant* (n\u0026thinsp;=\u0026thinsp;14)\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eCT-P13 SC initiated upfront (n\u0026thinsp;=\u0026thinsp;17)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 mg/kg\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e(2/3 infusions)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e120 mg every 2 weeks (n\u0026thinsp;=\u0026thinsp;6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e120 mg weekly (n\u0026thinsp;=\u0026thinsp;11)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e7\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCT-P13 SC switched from IV (n\u0026thinsp;=\u0026thinsp;22)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 mg/kg every 8 weeks (n\u0026thinsp;=\u0026thinsp;2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e120 mg every 2 weeks (n\u0026thinsp;=\u0026thinsp;2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e10 mg/kg every 8\u0026ndash;6\u0026ndash;4 weeks (n\u0026thinsp;=\u0026thinsp;20)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e120 mg weekly (n\u0026thinsp;=\u0026thinsp;9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e5\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e120 mg every 2 weeks (n\u0026thinsp;=\u0026thinsp;10)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e240 mg every 2 weeks (n\u0026thinsp;=\u0026thinsp;1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*Associated immunosuppressant: mercaptopurine, azathioprine\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\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 \u003cdiv class=\"SimplePara\"\u003eClinical remission data according to CT-P13 SC treatment protocol and disease activity at treatment initiation\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eClinical data on anoperineal disease at the time of CT-P13 SC initiation\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eCT-P13 SC initiated upfront\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003eCT-P13 SC switched from IV\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eActive APL\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e(n\u0026thinsp;=\u0026thinsp;17)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eAPL in remission\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e(n\u0026thinsp;=\u0026thinsp;0)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003eAPL in complte clinical remission\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e(n\u0026thinsp;=\u0026thinsp;20)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eAPL in partial clinical remission\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e(n\u0026thinsp;=\u0026thinsp;2)\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eClinical data at post-treatment evaluation\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAPL in complete clinical remission (n\u0026thinsp;=\u0026thinsp;29)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e11\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e18\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAPL in partial clinical remission (n\u0026thinsp;=\u0026thinsp;3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAPL with treatment failure (n\u0026thinsp;=\u0026thinsp;7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eDeep clinico-radiological remission data according to CT-P13 SC treatment protocols\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eClinico-radiological remission\u0026thinsp;=\u0026thinsp;no\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e(n\u0026thinsp;=\u0026thinsp;15)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eClinico-radiological remission\u0026thinsp;=\u0026thinsp;yes\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e(n\u0026thinsp;=\u0026thinsp;24)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003ep-value\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eProtocol according to treatment frequency\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.390\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eStandard\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e9 (60.0%)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e9 (37.5%)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIntensified\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6 (40.0%)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e15 (62.5%)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eProtocol according to treatment initiation strategy\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.413\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eUpfront\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e9 (60,0%)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e8 (33,3%)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSwitch from IV\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6 (40,0%)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e16 (66,7%)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eTherapeutic management according to clinical and pharmacokinetic data\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eTreatment persistence with the same frequency\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eIntensification by reducing injection intervals\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eTherapeutic change\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eUpfront SC protocol\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e120 mg every 2 weeks (n\u0026thinsp;=\u0026thinsp;6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e120 mg weekly (n\u0026thinsp;=\u0026thinsp;11)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSwitch from IV protocol\u003c/span\u003e\u003c/div\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e120 mg every 2 weeks (n\u0026thinsp;=\u0026thinsp;12)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e120 mg weekly or 240 mg every 2 weeks (n\u0026thinsp;=\u0026thinsp;10)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e8\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTotal (n\u0026thinsp;=\u0026thinsp;39)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e32 (82.0%)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (7.7%)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (10.3%)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\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":"digestive-diseases-and-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ddsj","sideBox":"Learn more about [Digestive Diseases and Sciences](http://link.springer.com/journal/10620)","snPcode":"10620","submissionUrl":"https://submission.nature.com/new-submission/10620/3","title":"Digestive Diseases and Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Crohn’s disease, Infliximab, CT-P13 SC, Anoperineal lesions, Anal fistulas","lastPublishedDoi":"10.21203/rs.3.rs-6264439/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6264439/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003cbr\u003e\nThe aim of this study was to evaluate the clinico-radiological remission rate in patients with fistulizing anoperineal lesions of Crohn's disease treated with CT-P13 SC, as well as pharmacokinetic data and treatment persistence rate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003cbr\u003e\nWe included all consecutive patients seen in the dedicated proctology outpatient clinic between June 1st and July 15th, 2024, for fistulizing anoperineal lesions and treated for at least 3 months with CT-P13 SC. Clinical, radiological and pharmacokinetic data were collected.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003cbr\u003e\nData from 39 patients were analyzed. The median duration of treatment was 16.1 months. Seventeen patients (43.6%) had received SC formulation from the start. The complete clinical remission rate was 74.4%, significantly higher in patients switched from IV to SC formulation. The deep radiological remission rate was 61.5%. The median infliximab concentration was 22.7 µg/mL. Only the intensified administration protocol impacted infliximab concentration. Immunosuppressants had no impact. The median infliximab concentration was higher in patients in remission (35.9 µg/mL versus 22.4 µg/mL), but without any significant difference. Among patients switched from IV to SC formulation, 86.5% maintained remission. In the overall study population, 89.7% were able to continue treatment, with intensified protocols in 61.5% of patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003cbr\u003e\nCT-P13 SC appears to be at least as effective as the IV formulation for fistulizing anoperineal lesions. Switching from IV to SC formulation seems more effective in achieving clinical remission. Despite numerically higher infliximab concentrations in patients in remission, no significant difference could be identified. Switching from IV to SC formulation was associated with maintenance of remission in 86.5% of cases.\u003c/p\u003e","manuscriptTitle":"Clinical, Radiological and Pharmacokinetic Data of CT-P13 Subcutaneous in Fistulizing Anoperineal Lesions of Crohn’s Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-16 08:49:25","doi":"10.21203/rs.3.rs-6264439/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-09T18:18:26+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-09T05:19:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222589572691865896246448573398725230776","date":"2025-04-16T18:46:34+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-26T22:26:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-25T19:36:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-20T08:04:27+00:00","index":"","fulltext":""},{"type":"submitted","content":"Digestive Diseases and Sciences","date":"2025-03-19T20:41:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"digestive-diseases-and-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ddsj","sideBox":"Learn more about [Digestive Diseases and Sciences](http://link.springer.com/journal/10620)","snPcode":"10620","submissionUrl":"https://submission.nature.com/new-submission/10620/3","title":"Digestive Diseases and Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"1b6234c1-f79a-438e-8df5-0ada8a423e3b","owner":[],"postedDate":"April 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-07T07:15:07+00:00","versionOfRecord":{"articleIdentity":"rs-6264439","link":"https://doi.org/10.1007/s10620-025-09210-9","journal":{"identity":"digestive-diseases-and-sciences","isVorOnly":false,"title":"Digestive Diseases and Sciences"},"publishedOn":"2025-07-25 15:57:46","publishedOnDateReadable":"July 25th, 2025"},"versionCreatedAt":"2025-04-16 08:49:25","video":"","vorDoi":"10.1007/s10620-025-09210-9","vorDoiUrl":"https://doi.org/10.1007/s10620-025-09210-9","workflowStages":[]},"version":"v1","identity":"rs-6264439","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6264439","identity":"rs-6264439","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}