Abstract INTRODUCTION Intestinal fibrosis is a serious complication of Crohn’s disease (CD) and is caused by the excess deposition of extracellular matrix (ECM) by intestinal myofibroblasts. Currently, there are no approved treatments. Identification of potential treatments is impeded by intestinal myofibroblasts being difficult to obtain and having a limited lifespan in vitro. Human intestinal organoids (HIOs) derived from induced pluripotent stem cells (iPSCs) contain a mesenchymal cell population that is analogous to intestinal myofibroblasts. iPSCs can be generated from peripheral blood mononuclear cells (PBMCs) and proliferate indefinitely meaning an unlimited number of patient-specific mesenchymal cells can be obtained. Our goal was to use our model of CD patients’ iPSC-derived mesenchymal (iPSC-MES) cells for high-throughput screening (HTS) and compare that their responses were similar to their paired intestinal fibroblasts of each patient. Methodology PBMCs and biopsy-derived (BD) ileal and colonic fibroblasts were obtained from 6 CD patients with a history of intestinal fibrosis. All PBMCs were reprogrammed to iPSCs, directed to HIOs and the mesenchymal cell population was purified. These cells were treated with TNFα/TGFβ (TT) for 48hrs to induce ECM deposition, and the antifibrotic potential of various therapeutics was examined. Selection of potential hits compared the z-score (z) of the compounds against baseline fibrosis (TTz=0), and a significant change was defined as a z ≥|±2|. Selected hits were then examined in BD ileal and colonic fibroblasts. RESULTS Our fibrosis model of iPSC-MES found a robust antifibrotic effect from the JAK1/2 inhibitor ruxolitinib (RXz=-4.91), in all 6 iPSC-MES lines. RX produced a significant reduction in ECM deposition in iPSC-MES cells (-34.81%) and similarly in patient matched BD-ileal (-53.76%) and -colonic fibroblasts (-43.14%) (Fig.1). Moreover, proteome enrichment analysis on iPSC-MES found that while TT produced a significant increase in a fibrosis-associated pathways, RX resulted in a decrease, namely: assembly of collagen fibrils (TTNES=4.80; RXNES=-2.83) and ECM organization (TTNES=5.39; RXNES=-2.65). We then evaluated other JAK inhibitors currently prescribed for the treatment of IBD: filgotinib (FG), tofacitinib (TF) and upadacitinib (UPA). While FG (-21.13%) and TF (-16.30%) showed a significant reduction in ECM, UPA (-39.22%) had the strongest antifibrotic activity, similar to RX (Fig.2). CONCLUSION We demonstrate the feasibility of utilizing iPSC-MES cells for HTS to identify potential antifibrotic therapies. This approach overcomes the limitations of biopsy-derived myofibroblasts, illustrates the potential utility of JAK inhibitors and thus opens up a new more feasible approach for studying precision-based treatments.

Abstract Background Filgotinib (FIL) is an oral, once-daily, Janus kinase 1 preferential inhibitor approved for the treatment of adults with moderately to severely active Ulcerative Colitis (UC)1. In the phase 2b/3 SELECTION trial, FIL demonstrated corticosteroid (CS)-sparing effects in patients with UC.2,3 Here, we aimed to characterise real-world systemic CS use in patients with UC receiving FIL. Methods GALOCEAN (NCT05817942) is an ongoing, European, multicentre, prospective, observational study of adults with UC receiving FIL in routine care; this interim analysis reports data up to week (W) 24. Baseline (BL) characteristics, systemic CS use during FIL treatment, and effectiveness outcomes through W24 were analysed for patients receiving FIL with BL CS use (FIL+CS) or without BL CS use (FIL–CS). Effectiveness outcomes assessed at BL, W10 and W24 were the partial Mayo Clinic Score (pMCS), two-item patient-reported outcome (PRO2) score and the proportion of patients in pMCS or PRO2 remission. Results As of 15 January 2025, 353 enrolled patients had BL data; 253 and 164 patients had data at W10 and W24, respectively. At BL, CS use was low; 93 out of 353 patients (26.3%) were in the FIL+CS group and 260 out of 353 patients (73.7%) were in the FIL–CS group. BL characteristics are summarized in Table I. Compared with FIL–CS, the FIL+CS group included a higher proportion of men (66.7% vs 45.8%) and more prior 5-aminosalicylate use (80.6% vs 69.2%), but fewer patients with prior exposure to advanced therapies (54.8% vs 79.6%). In the FIL+CS group, the proportion of patients using CS decreased from BL to 59.4% (41/69 patients) and 46.5% (20/43 patients) at W10 and at W24, respectively. A small number of patients in the FIL–CS group were using CS at W10 (4.4% [8/180] patients) and W24 (3.4% [3/88] patients) (Figure I). Improvements from BL in pMCS and PRO2 score were observed at W10 and W24 in both the FIL+CS and FIL–CS groups (Figure I). In addition, the proportion of patients in pMCS remission increased from 37.5% (24/64 patients) to 45.2% (19/42 patients) in the FIL+CS group and 43.0% (74/172 patients) to 57.6% (53/92 patients) in the FIL–CS group at W10 and W24, respectively. A similar pattern was observed for PRO2 remission (Figure I). Conclusion This real-world analysis showed that in the small number of patients with UC using CS at BL, over half were no longer using CS by W24 after initiating FIL. Patients achieved symptomatic remission and showed improvements in clinical symptoms over time following FIL treatment, irrespective of CS use at BL. These findings support that FIL treatment offers an opportunity for patients to reduce or minimise their CS use, consistent with results from the SELECTION trial.3

Abstract Background We aimed to compare the effectiveness of vedolizumab and filgotinib in patients with ulcerative colitis (UC) previously exposed to at least one anti-TNF agent. Methods This was a multicenter real-world evidence retrospective study that consecutively included all UC patients aged ≥18 years with symptomatic UC (partial Mayo score > 2) who initiated vedolizumab (VDZ) or filgotinib (FLG) after prior exposure to at least one anti-TNF. VDZ was administered intravenously with induction at 300 mg at weeks 0, 2, and 6, and subsequent IV infusions every 4 or 8 weeks according to the investigator’s choice. FLG was prescribed at a unique dose of 200 mg orally once daily. The primary endpoint was symptomatic remission (partial Mayo score ≤2) without corticosteroids (CFREM) at week 16 (W16). Secondary endpoints were clinical remission per modified Mayo score, and histological and endoscopic improvement (HEMI). Comparisons were made using propensity-score analyses (IPTW) adjusted the usual potential confounders. Results Overall, 230 patients were included (151 in the VDZ group and 79 in the FLG group. The two groups were comparable except for higher proportion of patients with prior exposure to at least 2 biologics (36.1% vs 92.1%; p < 0.001) in FLG group and concomitant corticosteroids (31.1% vs 19.0%) or an associated immunosuppressant (20.5% vs 0%) in VDZ group. After propensity adjustment, CFREM at W16 was achieved in 38.1% and 31.1% of patients in VDZ and FLG groups, respectively (p = 0.51). Subgroup analyses (after IPTW) showed that VDZ was more effective than FLG after failure of a single biologic (p < 0.001), with no difference after two prior failures (OR = 2.05 [0.36–11.71], p = 0.41), whereas FLG was more effective after failure of at least three prior biologics (OR = 10.4 [1.1–102.4], p = 0.045). No predictor of FLG effectiveness was identified. Factors associated with absence of CFREM at W16 on VDZ were UC severity (p = 0.035), failure of ≥ 3 biologics (p = 0.013), and primary failure to at least one biologic (p = 0.013). No difference was observed between the two treatments regarding clinical remission and HEMI at W16 (p = 0.47 and 0.18, respectively). With a median follow-up of over 12 months, no significant differences were noted between the two treatments in time to treatment discontinuation, UC-related hospitalization, or colectomy. Conclusion In this real-world evidence study, VDZ appeared to be a more effective option than FLG as a second-line biologic (after anti-TNF failure), whereas FLG became a better option in third- or fourth-line of advanced therapies. These data may help physicians managing patients with UC to guide therapeutic decision-making. Conflict of interest: Prof. Dr. Buisson, Anthony: Consulting fees from: Abbvie, AlfaSigma, Amgen, Arena, Biogen, Celltrion, CTMA, Ferring, Galapagos, Guty Care, Janssen, Hikma, Lilly, Mylan, Nexbiome, Pfizer, Roche, Takeda, Tillotts Lecture fees from: Abbvie, AlfaSigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Hikma, Janssen, Lilly, Mayoli-Spindler, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor-Pharma Research fundings from: Abbvie, AlfaSigma, Celltrion, Janssen, Lessaffre, Lilly, Pfizer, Takeda Bouguen, Guillaume: Grant: Abbvie, Ferisinus Personal Fees: Abbvie, Takeda, Fresinus, Amgen, Biogène, Arena, Ferring, Gilead, Janssen, MSD, Pfizer, Sandoz, Takeda, Tillots, Vifor pharma Nachury, Maria: Abbvie, Alfa Sigma, Biosynex, Celltrion, Galapagos, Janssen, Lilly, MSD, Pfizer, Takeda Uzzan, Mathieu: Grant: ECCO-IOIBD, Fondation pour la Recherche Medicale (FRM), SNFGE Personal Fees: Abbvie, Takeda, Celltrion, Janssen, Amgen, Alfasigma, Pfizer Domas, Quentin: No conflict of interest Serrero, Melanie: No conflict of interest Altwegg, Romain: Advisory boards from Abbvie, Takeda, Johnson and Johnson, Lilly, Alphasigma, Celltrion, Pfizer, Amgen, Biogen, Sandoz, Ferring Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Amiot, Aurelien: Personal Fees: Abbvie, Fresenius-Kabi, Adacyte, Tillotts pharma, Janssen, Pfizer, Biogen, AMgen, Sandoz, Takeda, Galapagos, Eli Lilly Caillo, Ludovic: Abbvie, Amgen, Celltrion, Ferring, Fresenius, Lilly, Jonhson&Jonhson, MSD, Pfizer, Takeda, Sandoz Hupé, Marianne: No conflict of interest Gilletta de Saint Joseph, Cyrielle: Speaker/ consultant fees from Abbvie, AlfaSigma, Amgen, Celltrion, Ferring, Fresenius, Janssen, Lilly, Pfizer, Takeda and Tillots Treton, Xavier: Personal Fees: Lectures and advisory board : Abbvie, Celltrion, MSD, johnson&Johnson, Takeda, Amgen, Alphasigma, Lilly, Pfizer Other: participations: Thabor Therapeutics Pereira, Bruno: No conflict of interest

Abstract Background Filgotinib (FIL) is an oral, once-daily, Janus kinase 1 preferential inhibitor approved for the treatment of moderately to severely active Ulcerative Colitis (UC).1,2 We evaluated the real-world effectiveness of FIL by prior use of advanced treatment (AT) and predictors of clinical response in UC. Methods GALOCEAN (NCT05817942) is an ongoing, European, multicentre, prospective, observational study of adults with UC receiving FIL in routine care; this interim analysis reports data up to week (W) 24. Effectiveness outcomes (partial Mayo Clinic Score [pMCS] and the two-item patient-reported outcome [PRO2] score) were analysed by prior use of AT (AT-naive, 1, 2 or ≥ 3 ATs). Health-related quality of life (HRQoL) outcomes (defined in Table I) were analysed at baseline (BL), W10 and W24. Data are reported as descriptive statistics. Univariate and multivariate logistic regression analyses assessed BL characteristics predictive of pMCS and PRO2 remission at W10. Results As of 15 January 2025, there were 353 enrolled patients with available BL data; 253 and 164 patients had data at W10 and W24, respectively. At BL, 26.9% (95/353) of patients were AT-naive and 27.8% (98/353), 24.6% (87/353) and 20.7% (73/353) had previously received 1, 2 or ≥ 3 ATs, respectively. BL characteristics are shown in Table I. The pMCS and PRO2 score improved from BL to W10 and from BL to W24 for all subgroups, with the largest improvement in the AT-naive group (Figure I). The proportions of patients in pMCS and PRO2 remission were numerically highest for the AT-naive subgroup versus the 1, 2 and ≥3 AT subgroups at W10 and W24 (Figure I). All HRQoL outcomes improved from BL by W10 and W24, irrespective of prior AT. Several BL characteristics were predictive of pMCS remission (predictor vs comparator: prior AT [naive vs experienced], Urgency NRS [none/mild vs moderate/severe] and pMCS at BL; p<0.05) and PRO2 remission (prior AT [naive vs experienced], FACIT-Fatigue score [mild vs moderate/severe] and PRO2 score at BL; p<0.05) at W10. Conclusion In the real-world GALOCEAN study, FIL showed sustained effectiveness regardless of prior AT use, with the greatest estimated benefit in AT-naive patients with UC. HRQoL at BL was severely impaired for many patients, which improved after FIL initiation, regardless of prior AT use. Being naive to AT and having symptoms associated with moderate disease at BL was predictive of both pMCS and PRO2 remission at W10. These results are consistent with findings from the SELECTION trial, which suggest that BL characteristics may predict clinical outcomes with FIL.2-4

ObjectivesTo compare the 2-year clinical effectiveness of the four globally approved Janus kinase inhibitors (JAKis; tofacitinib (TOF), baricitinib (BAR), upadacitinib (UPA) and filgotinib (FIL)) in patients with rheumatoid arthritis (RA) in real-world settings.MethodsThis retrospective cohort study used data from FIRST registry, a multicentre registry of patients with RA. The primary endpoint was the change in Clinical Disease Activity Index (CDAI) score at year 2. Secondary endpoints included changes in individual CDAI components, patient-reported outcomes (PROs) and reasons for JAKi discontinuation. Multivariable mixed-effects models adjusted for baseline characteristics were used to compare the four JAKis.ResultsA total of 607 treatment courses with JAKis (TOF: 159, BAR: 262, UPA: 122, FIL: 64) were included. Baseline characteristics differed notably among treatment groups: UPA and FIL were frequently used as the second-line JAKis for older patients with comorbidities. The 2-year overall retention rate was 78%. The most common reason for discontinuation was insufficient effectiveness, with 6.5/100 person-years (py), followed by adverse events of 4.2/100 py. As-observed analysis demonstrated the slower improvement in the UPA and FIL groups. However, multivariable analysis revealed no significant differences in CDAI or PROs. The UPA group demonstrated greater improvement in two CDAI components: tender joint count and evaluator’s global assessment.ConclusionThis real-world study found no clinically meaningful differences in 2-year effectiveness among four JAKis, although the study was not powerful enough to detect differences in safety. Further long-term, real-world data are needed to evaluate the safety of these agents and refine their risk-benefit profiles.

Abstract Background JAK inhibitors (JAKi) are small molecules that cross the placenta from early pregnancy.1 Evidence on the safety of in utero JAKi exposure remains limited, particularly regarding pregnancy outcomes, infant infections, vaccine responses, and early development.2, 3 Methods We conducted a multicenter retrospective study within the ECCO CONFER network, including pregnant women with inflammatory bowel disease (IBD) exposed to tofacitinib (TOFA), upadacitinib (UPA), or filgotinib (FILGO). Data were collected from 22 centers across 16 countries and included maternal characteristics, disease activity, medication patterns, and pregnancy and infant outcomes. Results Among 55 JAKi exposed pregnancies, 21 (38.2%) were unplanned and 30 (54.6%) had active disease. Nine women (16.4%) initiated JAKi during pregnancy. Overall, 38 (69.1%) received TOFA, 15 (27.3%) UPA, and 2 (3.6%) FILGO; 39 (70.9%) continued treatment throughout pregnancy. JAKi discontinuation in 1st-2nd trimester led to disease activity in 9/16 cases (56.3%). Maternal complication risk was low: no DVT or (pre) eclampsia occurred; three cases of premature rupture of membranes (GA 34–37) and four required hospitalizations due to infection or other complications. A total of 10 abortions occurred - five spontaneous (9.1%) and five induced (9.1%), including three due to concern about JAKi exposure. Among 45 live births, two infants (3.6%) were preterm, four (7.3%) small for gestational age, and two (3.6%) had Apgar <7 at 5 minutes. No congenital abnormalities were reported. Infant follow-up findings are summarized in Table 1. One-third of breastfeeding women continued JAKi postpartum. A high adherence rate to the national immunization schedule was seen. Eight (19.5%) received the live BCG-vaccine within the first 30 days of life. No adverse events followed live or inactivated vaccines, and no malignancies were observed. Conclusion In this global cohort of JAKi-exposed pregnancies in women with IBD, maternal complication rates were low, and no increased risk of adverse outcomes among live births was identified. While disease activity was common, particularly following discontinuation of JAKi, infant outcomes - including development, infection risk, and vaccine response - were reassuring. These findings provide important preliminary safety data to inform decision-making regarding JAKi use in pregnancy, though prospective studies are needed to confirm long-term safety.

Abstract Background Cytomegalovirus (CMV) colitis mimics acute IBD flares, making it a critical differential diagnosis in acute severe colitis (ACS). Therefore, it’s an important differential diagnosis in patients with ACS. Prevalence ranges from 10 to 30% in steroid-refractory ulcerative colitis (UC).1,2 Corticosteroids are identified as risk factors for CMV colitis. Evidence for biologics and small molecules remains conflicting or absent.1 This study aimed to evaluate demographic data of CMV colitis in a central European inflammatory bowel disease (IBD) cohort. Methods We conducted a retrospective analysis of 110 colon biopsy samples of IBD patients with clinical suspicion of CMV colitis at our IBD center between 2020 and 2024. All biopsies were obtained from the most inflamed colonic segments during diagnostic colonoscopy. CMV testing including immunohistochemistry (IHC) and quantitative tissue PCR (qPCR) was performed at the affiliated pathology and virology departments. CMV positivity was defined as IHC+/qPCR-, IHC-/qPCR+ or IHC+/qPCR+.3 Results A total of 110 IBD patients with clinical suspicion of CMV colitis were included. The median age was 43.5 years [IQR 36-57]. Gender distribution was nearly equal: 50.9% male (56/110) and 49.1% female (54/110). The majority had UC 75.5% (83/110), followed by Crohn’s colitis (CC) 23.6% (26/110), and colitis indeterminata (1/110). The overall prevalence of CMV colitis was 16.4% (18/110). Among CMV-positive cases 94.4% (17/18) had UC and 5.6% (1/18) had CC. Among the 18 CMV-positive patients, current immunosuppressive therapy included systemic glucocorticoids (GC) 33.3% (6/18), VDZ 27.8% (5/18), Updadacitinib (UPA) 22.2% (4/18), Ustekinumab (UST) 11.1% (2/18), Adalimumab (ADA) 5.6% (1/18), Filgotinib (FILGO) 5.6% (1/18), and topical GCs 5.6% (1/18). 94.4% (17/18) of CMV positive patients had a history of prior systemic immunosuppressive therapy. Of those, 6 never received a biologic, 5 received 1 biologic, 3 received 2 biologics, and 4 received ≥3 biologics. 61.1% (11/18) CMV-positive patients had a documented prior episode of CMV colitis. Conclusion The prevalence of CMV-colitis was 16.4% among IBD patients with clinical suspicion, predominantly affecting those with UC (94.4%). Nearly all positive cases had prior or current immunosuppressive exposure, mostly systemic GCs (33.3%), VDZ (27.8%) or JAK inhibitors (UPA/FILGO 27.8%). Notably, 61.1% had a documented prior episode of CMV colitis. These findings highlight, that immunosuppressed patients – particularly those with UC are at elevated risk of a CMV colitis. Further studies are needed to identify IBD patients and immunosuppressive therapies associated with the highest risk of CMV colitis.

IntroductionThe efficacy and safety of filgotinib (FIL) for the treatment of patients with rheumatoid arthritis (RA) have been evaluated in a number of randomized controlled trials. However, there is a scarcity of real-world studies evaluating the effectiveness, persistence, tolerability, and safety of FIL in everyday clinical practice. This study aimed to assess the effectiveness and retention rate of FIL in a real-world cohort of patients with RA.MethodsA multicenter retrospective cohort study of patients with RA treated with FIL was conducted in 27 Italian tertiary referral rheumatology centers. The drug retention rate (DRR) was estimated by the Kaplan–Meier method, while multivariate Cox regression was used to detect potential factors affecting drug survival and persistence in therapy. Disease activity score (DAS28-CRP) was assessed at baseline and after 6 and 12 months.ResultsWe enrolled 204 patients (80% female). The DRR of FIL was 90.2% (95% confidence interval (CI) 86–94.6%), 75.1% (95% CI 68.5–82.4%), and 64.7% (95% CI 56.3–74.3%) at months 6, 12, and 18, respectively. The DRR was negatively associated with the line of treatment and the presence of rheumatoid factor. Effectiveness was evaluated as DAS28-CRP response. At 6 months, DAS28-CRP remission was observed in 65 (36.1%) patients, and remission or low disease activity in 98 (54.4%). At 12 months, DAS28-CRP remission was observed in 64 (50.0%) patients, and remission or low disease activity in 81 (63.2%).ConclusionsThis analysis of real-world patients with RA demonstrated the effectiveness of FIL with a good DAS28-CRP response and high DRR at follow-up.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-025-00805-2.

Background and aim: Tofacitinib (TOF), filgotinib (FIL), and upadacitinib (UPA) are approved Janus kinase inhibitors (JAKis) for ulcerative colitis (UC), but real-world comparative data remain limited. This study assessed their efficacy, persistence, and safety in regional Japanese hospitals.Methods: We retrospectively analyzed 148 UC treatment sessions (TOF, 60; FIL, 53; UPA, 35). The primary outcome was clinical remission (partial Mayo score ≤1 with rectal bleeding score 0). Secondary outcomes included clinical response, steroid-free remission, and treatment persistence. Adverse events and biologics (Bio)/JAKi subgroup data were collected.Results: At week 8, clinical remission rates were similar for TOF (46%), FIL (44%), and UPA (46%). At week 24, FIL had the highest remission rate (61%) vs. TOF (46%) and UPA (41%), a trend that continued at week 48 (59%, 41%, 44%). FIL also showed the highest remission in both Bio/JAKi-naïve and failure sessions at weeks 24 and 48. UPA had the highest clinical response at week 8 (67%). TOF showed stable remission over time (46%, 46%, 41%). Steroid-free remission was more frequent with FIL at weeks 24 (61%) and 48 (59%) than with TOF (46%, 41%) or UPA (35%, 33%). Persistence was similar across agents through week 24. Safety profiles aligned with prior data, though rare events such as Pneumocystis jirovecii pneumonia and interstitial pneumonia were noted.Conclusions: FIL showed favorable remission rates, especially in Bio/JAKi-naïve patients, and remained effective after prior failures, suggesting broad applicability. UPA and TOF showed similar remission rates in our cohort.

The rising incidence of ulcerative colitis (UC) globally highlights the necessity for treatment strategies that extend beyond symptom control to include inducing and maintaining remission, achieving biochemical and endoscopic remission, and restoring quality of life. Janus kinase inhibitors, such as filgotinib (FIL), show promise in treating UC. This review consolidates evidence on FIL in treating UC from the SELECTION and SELECTIONLTE trials, and real-world studies. Overall, FIL demonstrated rapid symptom relief (e.g., improved rectal bleeding and stool frequency) within 7 days and durable efficacy (e.g., clinical remission, Mayo Clinic Score response) up to 4 years. Improvements in health-related quality of life (HRQoL) and reduced corticosteroid dependency were also observed. The 200 mg dose generally elicited greater efficacy responses than the 100 mg dose, and hence may potentially be a more suitable choice for optimizing treatment outcomes. Although FIL may be an effective long-term treatment option regardless of prior biologic experience, biologic-naive patients may experience greater sustained clinical improvements. Safety outcomes indicated that FIL was well tolerated with no unexpected safety signals in SELECTION and SELECTIONLTE. These findings support FIL's potential as a robust therapeutic option for UC, due to its acceptable safety profile and benefits across clinical and HRQoL outcomes.

Real-world data on the use of filgotinib (FILGO) in patients with ulcerative colitis (UC) are limited. This study aims to provide consistent results on the effectiveness and safety of FILGO in treating UC. A retrospective assessment of clinical and endoscopic activity was conducted in a cohort of patients with UC according to the full Mayo score. The primary co-endpoints of the study were the evaluation of the effectiveness and safety of FILGO. We enrolled 102 patients with a median follow-up of 24 weeks (interquartile range, 8-24 weeks). At 8 weeks and the end of follow-up, clinical remission was achieved by 38 (37.2%) and 47 (46.1%) patients, respectively. Clinical remission was achieved in 13 of 18 patients (72.2%) receiving first-line therapy, 7 of 19 patients (36.8%) receiving second-line therapy, and 27 of 65 patients (41.5%) receiving third-line therapy (P= 0.002). Clinical remission at 8 weeks predicted clinical remission at the end of follow-up (P= 0.021). Age > 40 years (P= 0.046) and being on second- or third-line of treatment (P= 0.005) were negative predictors for clinical remission. Seventy-one patients (69.6%) achieved a clinical response. At endoscopic evaluation, mucosal healing was observed in 18 out of 30 patients (60.0%). Steroid-free remission was present in 38 out of 46 patients (82.6%). Five patients (4.9%) needed colectomy. Adverse events were recorded in 6 patients (5.8%): 2 cases (2%) were severe, requiring discontinuation of FILGO. Our real-world data confirms that FILGO is safe and effective for patients with UC. Its efficacy is significantly improved when used as a first-line treatment.

Filgotinib (FIL), a Janus kinase inhibitor, shows clinical efficacy in moderate to severe ulcerative colitis (UC), but no prospective studies have examined endoscopic and histopathological outcomes. This study aimed to evaluate the therapeutic efficacy of FIL in moderate to severe UC using the Partial Mayo Score (PMS), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Geboes Histopathology Score (GHS). Twenty-two patients with clinically moderate to severe refractory UC were enrolled. Remission was defined as PMS 0, UCEIS 0, and GHS < 2.0 (sigmoid and rectum). Achievement rates were prospectively evaluated at 12, 24, and 52 weeks after FIL initiation compared to baseline. Among the 22 patients, comprising Biologic-Naïve (BN, n = 12) and Biologic-Experienced (BE, n = 10) cohorts, achievement rates were highest for PMS 0, followed by UCEIS 0, and lowest for GHS < 2.0. Partial Mayo Score 0 achievement for BN/BE was 75% (P = .001)/50% (P = .031) at 12 weeks, 75% (P = .003)/70% (P = .016) at 24 weeks, and 75% (P = .002)/70% (P = .016) at 52 weeks. Ulcerative Colitis Endoscopic Index of Severity 0 achievement for BN/BE was 58.3% (P = .008)/20% (P = .016) at 12 weeks, 41.6% (P = .019)/40% (P = .016) at 24 weeks, and 50% (P = .002)/50% (P = .016) at 52 weeks. Geboes Histopathology Score < 2.0 (sigmoid) achievement for BN/BE was 25%/0% at 12 weeks, 33.3%/10% at 24 weeks, and 25%/10% at 52 weeks. Geboes Histopathology Score < 2.0 (rectum) achievement for BN/BE was 50%/0% at 12 weeks, 41.6%/20% at 24 weeks, and 33.3%/40% at 52 weeks. Filgotinib appears to be an effective treatment for UC, demonstrating potential for achieving not only clinical remission but also endoscopic and histopathological remission.

Abstract Background/Aims Filgotinib (FIL) is a Janus kinase 1 preferential inhibitor for the treatment of moderate to severe rheumatoid arthritis (RA). This post hoc, interim analysis of FINCH 4 (NCT03025308) characterizes the long-term efficacy of FIL administered as monotherapy or combination therapy. Methods Patients enrolled in FINCH 4 (from FINCH 1, 2, and 3) were pooled and assessed according to treatment group: FIL 200 mg (FIL200) or FIL 100 mg (FIL100), administered as monotherapy or combination therapy. Combination therapy and monotherapy were defined as FIL with and without concurrent methotrexate or other conventional synthetic disease-modifying antirheumatic drug from baseline of FINCH 4 for the duration of the study, respectively. Patients who switched from combination to monotherapy for ≤28 days were included in the combination therapy arm. Least-squares (LS) mean change from baseline of the parent study in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) was analyzed using a mixed-effects model for repeated measures, including variables for: parent study baseline value, parent study, prior exposure to FIL (binary), treatment, visit and treatment by visit interaction. The nonstratified response rates of DAS28-CRP &amp;lt;2.6 and ≤3.2 were analyzed based on observed cases (OC) and nonresponder imputation (NRI). Results Database cutoff was May 8, 2023. A total of 2,273 patients were included in the analyses (771 patients received FIL200 combination therapy, 520 received FIL200 monotherapy, 728 received FIL100 combination therapy and 254 received FIL100 monotherapy). At Week 216, LS mean change (95% confidence interval) from baseline of the parent study in DAS28-CRP was -3.0 (-3.1, -2.9) in the FIL200 combination therapy arm, -3.3 (-3.4, -3.2) in the FIL200 monotherapy arm, -2.8 (-2.9, -2.7) in the FIL100 combination therapy arm and -2.9 (-3.1, -2.7) in the FIL100 monotherapy arm. Based on the NRI analysis, DAS28-CRP &amp;lt;2.6 was achieved by 27.1% in the FIL200 combination therapy arm, 25.6% in the FIL200 monotherapy arm, 21.6% in the FIL100 combination therapy arm and 20.5% in the FIL100 monotherapy arm. With the OC analysis, the corresponding proportions were 60.2%, 73.5%, 50.2% and 60.5%, respectively. The proportion of patients to achieve DAS28-CRP ≤3.2 in the FIL200 combination therapy, FIL200 monotherapy, FIL100 combination therapy, and FIL100 monotherapy arms was 35.4%, 30.4%, 30.9% and 24.8%, respectively, with the NRI analysis, and 78.7%, 87.3%, 71.9% and 73.3%, respectively, with the OC analysis. Conclusion This post hoc, interim analysis of FINCH 4 shows that improvements in disease activity (DAS28-CRP) with FIL treatment were maintained over time, regardless of whether FIL was administered as monotherapy or as combination therapy. Disclosure M. Buch: Consultancies; Abbvie, Arxx Therapeutics, Boehringer Ingelheim, CESAS medical, Galapagos, Gilead, Pfizer. Member of speakers’ bureau; Abbvie. Grants/research support; Galapagos, Gilead. P. Verschueren: Consultancies; Abbvie, Eli Lilly, Galapagos. Member of speakers’ bureau; Eli Lilly, Galapagos. Grants/research support; Galapagos, Pfizer. R. Caporali: Consultancies; Abbvie, Accord, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, Novartis, Pfizer, UCB. Member of speakers’ bureau; Abbvie, Amgen, BMS, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB. T. Huizinga: Consultancies; BMS, Eli Lilly, Galapagos, Pfizer. Member of speakers’ bureau; BMS, Eli Lilly, Galapagos. Grants/research support; Received by the Department of Rheumatology, Leiden University, in the context of IMI projects. E. Omoruyi: Consultancies; Galapagos, Janssen. Shareholder/stock ownership; UCB. D. De Vries: Shareholder/stock ownership; Galapagos. Other; Employed by Galapagos. J. Ritsema: Shareholder/stock ownership; Galapagos. Other; Employed by Galapagos. F. De Leonardis: Shareholder/stock ownership; Galapagos. Other; Employed by Galapagos. D. Aletaha: Consultancies; Abbvie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, Sanofi. Member of speakers’ bureau; Abbvie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, Sanofi. Grants/research support; Abbvie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, Sanofi.

Abstract Background/Aims Filgotinib (FIL) is a Janus kinase 1 preferential inhibitor for the treatment of moderate to severe rheumatoid arthritis (RA) approved at doses of 100 mg (FIL100) and 200 mg (FIL200). This integrated safety analysis provides an update on selected treatment-emergent adverse events for FIL up to a median (maximum) exposure of 4.3 (8.3) years. Methods FIL rheumatoid arthritis data were integrated from 7 clinical trials: the Phase 2 DARWIN studies (NCT01888874, NCT01894516), the Phase 3 FINCH studies (NCT02889796, NCT02873936, NCT02886728), and the long-term extension studies DARWIN 3 (NCT02065700) and FINCH 4 (NCT03025308). Exposure-adjusted incidence rates (EAIRs)/100 patient-years of exposure (PYE), censored at time of first event, were determined for major adverse cardiovascular events (MACE), venous thromboembolism (VTE), arterial systemic thromboembolism (ASTE), nonmelanoma skin cancer (NMSC), malignancies (excluding NMSC), herpes zoster, serious infections and deaths. Data were from completed studies and up until May 8, 2023, for FINCH 4. Results In total, 3,691 patients received FIL with a total exposure of 14,127 PYE. Median (maximum) exposure was 4.3 (8.3) years in the pooled FIL group; 3.6 (8.1) years for FIL100 and 4.4 (8.3) years for FIL200. Baseline demographics and disease characteristics were balanced between the dose groups. Incidences of adverse events of special interest (AESIs), including MACE, VTE, ASTE, NMSC, malignancies (excluding NMSC), serious infections, herpes zoster and all-cause mortality, were comparable between the data cut in 2022 and the current analysis (Table 1). The EAIR (95% confidence interval [CI])/100 PYE of serious infections was 2.2 (1.8, 2.6) and 1.7 (1.5, 2.0) in the FIL100 and FIL200 dose groups, respectively. The EAIR (95% CI)/100 PYE of herpes zoster was 1.1 (0.8, 1.4) for FIL100 and 1.4 (1.2, 1.7) for FIL200 (Table 1). Over 312 weeks, the risk of all-cause mortality was similar for FIL100 and FIL200. Conclusion In this updated integrated safety analysis, the safety profile of FIL remained stable over time and similar to that from the previous analysis. No new safety information concerning AESIs were identified in the overall RA population. Disclosure K.L. Winthrop: Consultancies; Abbvie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB. Grants/research support; BMS, GSK. D. Aletaha: Consultancies; Abbvie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, Sanofi. Member of speakers’ bureau; Abbvie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, Sanofi. Grants/research support; Abbvie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, Sanofi. R. Caporali: Consultancies; Abbvie, Accord, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, Novartis, Pfizer, UCB. Member of speakers’ bureau; Abbvie, Amgen, BMS, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB. Y. Tanaka: Member of speakers’ bureau; Abbvie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho and Taisho. Grants/research support; Chugai, Eisai, Mitsubishi Tanabe, Taisho. T. Takeuchi: Consultancies; Abbvie, Astellas, Chugai, Eli Lilly, Gilead, Janssen, Mitsubishi Tanabe, Pfizer. Member of speakers’ bureau; Abbvie, AYUMI, BMS, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Mitsubishi Tanabe, Pfizer, Sanofi. Grants/research support; Abbvie, Asahi Kasei Pharma, Astellas, AYUMI, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Mitsubishi Tanabe, Nippon Kayaku, UCB. M. Buch: Consultancies; Abbvie, Arxx Therapeutics, Boehringer Ingelheim, CESAS medical, Galapagos, Gilead, Pfizer. Member of speakers’ bureau; Abbvie. Grants/research support; Galapagos, Gilead. Other; Professor Maya Buch is a non-Author presenter. V. Modgill: Shareholder/stock ownership; Galapagos. Other; Employed by Galapagos. E. Omoruyi: Consultancies; Galapagos, Janssen. Shareholder/stock ownership; UCB. Other; Employed by Galapagos. D. De Vries: Shareholder/stock ownership; Galapagos. Other; Employed by Galapagos. K. Van Beneden: Shareholder/stock ownership; Galapagos. Other; Employed by Galapagos. J. Gottenberg: Consultancies; Abbvie, BMS, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer. Grants/research support; BMS, Pfizer. G. Burmester: Consultancies; Abbvie, BMS, Galapagos, Eli Lilly, MSD, Pfizer. Member of speakers’ bureau; Abbvie, BMS, Galapagos, Eli Lilly, MSD, Pfizer.

Filgotinib (FLG) is a Janus kinase 1 inhibitor and is metabolized to an active metabolite, GS-829845. There is no report on the method for simultaneous quantification of FLG and GS-829845 in clinical samples. We developed a liquid chromatography-tandem mass spectrometry method for simultaneous determination of FLG and GS-829845 in patient plasma. FLG and GS-829845 were extracted from an aliquot of 50 μL of human plasma by simple deproteinization using methanol. Chromatographic separation was performed using a Shim-pack Scepter C18-120 column with a combined mobile phase of water and methanol containing 0.1% formic acid and gradient elution at a flow rate of 0.2 mL/min. Detection was performed by positive electrospray ionization using a QTRAP 4500 mass spectrometer. The method was validated in the concentration range of 2.5-50 ng/mL for FLG and 250-5000 ng/mL for GS-829845. Intra- and inter-day assay accuracy and precision were within 11.4% and 13.9%, respectively. Recoveries and matrix effects were consistent and reproducible. This developed and fully validated method is simple, rapid, and cost-effective and was used successfully for therapeutic drug monitoring in a patient with rheumatoid arthritis.

Background/Aims Tofacitinib (TFB), filgotinib (FIL), and upadacitinib (UPA) are Janus kinase (JAK) inhibitors approved for moderate-to-severe ulcerative colitis (UC). The appropriate positioning of each JAK inhibitor in the treatment algorithm, however, is unclear. Furthermore, real-world efficacy of JAK inhibitors for patients with UC and prior anti-tumor necrosis factor α antibody (aTNF) treatment are not fully investigated. We compared the efficacy and safety of 3 JAK inhibitors in patients with UC, considering their prior aTNF exposure. Methods A retrospective study was conducted in patients with UC who started TFB, FIL, or UPA at 2 academic centers. This propensity score-matched cohort study assessed the effectiveness of the 3 JAK inhibitors for UC in patients with and without prior aTNF exposure, comparing steroid-free clinical remission and response rates after 8 weeks. Results Among 274 patients who met the inclusion criteria, 145 experienced aTNF exposure (TFB: 59.2%, 100/169; FIL: 34.5%, 20/58; UPA: 53.2%, 25/47). Based on propensity score-matching, UPA led to a higher steroid-free clinical remission rates than TFB (adjusted odds ratio [aOR], 5.57; 95% confidence interval [CI], 1.42–21.90) or FIL (aOR, 9.00; 95% CI, 1.42–57.10) in patients exposed to aTNF. Steroid-free clinical remission and clinical response rates did not differ significantly between each group in patients non-exposed to aTNF. The incidence of adverse events was slightly higher with UPA than TFB or FIL. Conclusions UPA may be more effective for UC than TFB or FIL, especially in patients with previous aTNF exposure, although consideration should be given to adverse events.

Abstract Background Filgotinib (FIL), a once-daily, oral Janus kinase 1 preferential inhibitor, was approved for the treatment of Ulcerative Colitis (UC) following the phase 2b/3, randomized SELECTION clinical trial.1 Real-world data on the effectiveness and safety of FIL are needed to complement the results of clinical trials for applicability in daily clinical practice. Methods GALOCEAN (NCT05817942) is a European, multicenter, prospective, observational study that will recruit ~600 adults with UC receiving FIL in clinical care. In this interim analysis, we report data for up to 24 weeks. Effectiveness outcomes were the Mayo Clinic Score (MCS), the partial MCS (pMCS) and the two-item patient-reported outcome (PRO2) score, as well as Short Inflammatory Bowel Disease Questionnaire (SIBDQ), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and Urgency Numerical Rating Scale (NRS) scores. Safety assessments included treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESIs). Data were analyzed for the overall patient group, and for those receiving FIL without baseline concomitant therapies (FIL−ct) or FIL with baseline concomitant therapies (FIL+ct; including conventional therapies, biologics and synthetic targeted small molecules). Results As of June 2024, 277 patients had been enrolled in GALOCEAN. Of these, 223 had available baseline data; 139 and 83 completed 10 and 24 weeks of treatment, respectively. At baseline, 53% of patients (118/223) received FIL−ct and 47% (105/223) received FIL+ct, of whom 92.4% (97/105) received aminosalicylates. Baseline characteristics are shown in Table 1. MCS, pMCS, PRO2, SIBDQ, FACIT-Fatigue and Urgency NRS data are shown in Table 2. At week 24, remission was achieved by 30% of patients (FIL−ct, 29%; FIL+ct, 31%) for the MCS, 47% (FIL−ct, 47%; FIL+ct, 47%) for the pMCS and 50% (FIL−ct, 44%; FIL+ct, 55%) for the PRO2 score. At week 24, minimal clinically important differences (MCIDs) were achieved by 66% of patients (FIL−ct, 75%; FIL+ct, 58%) for the SIBDQ score, 64% (FIL−ct, 72%; FIL+ct, 57%) for the FACIT-Fatigue score and 43% (FIL−ct, 50%; FIL+ct, 36%) for the Urgency NRS score. Overall, 30% of patients (FIL−ct, 25%; FIL+ct, 36%) had ≥1 TEAE and 6% (6% in each subgroup) had ≥1 AESI. Conclusion This study highlights the overall effectiveness and safety profile of filgotinib up to 24 weeks in a real-world cohort, both when used alone or with concomitant therapy. The safety profiles were consistent with previous data. The GALOCEAN study is ongoing.

Abstract Background As no direct comparisons exist, we compared the effectiveness of tofacitinib (TOFA), filgotinib (FILGO) and upadacitinib (UPA) in patients with Ulcerative Colitis (UC). Methods In this retrospective multicenter study, we included all consecutive patients with UC ≥18 years-old, partial Mayo score &amp;gt; 2 who had started TOFA, FILGO or UPA after receiving ≥ 1 biologic. Following regimen were applied : TOFA (10mg b.i.d --&amp;gt; at W8: 5mg or 10 mg b.i.d according to physician’s judgement), FILGO (200mg q.d) and for UPA (45mg q.d --&amp;gt; at W8: 45mg, 30 mg or 15 mg q.d according to physician’s judgement). The primary endpoint was symptomatic remission (partial Mayo score ≤ 2) without corticosteroids (CFREM) at W16. Secondary endpoints were clinical-endoscopic remission (CFREM + endoscopic Mayo score ≤ 1), histological-endoscopic mucosal improvement (HEMI) (= clinical-endoscopic and histological remission (Nancy index ≤ 1)), drug retention and secondary loss of response. Comparisons were performed using propensity scores adjustment (IPTW). Results Overall 290 UC patients were included: TOFA=150, FILGO=79, UPA=61. The 3 groups were comparable except for higher proportion of patients with partial Mayo score &amp;gt; 6 or prior exposure &amp;gt; 3 biologics in UPA group (p &amp;lt; 0.001). Recommended maintenance dose (TOFA 5mg b.i.d/UPA 30 mg/FILGO 200 mg) from W8 after response to induction was applied in 41.3% (62/150), 65.8 % (52/79), and 59.0% (36/61), in TOFA, FILGO and UPA groups, respectively, and failed (need for dose re-escalation/drug discontinuation/no clinical remission at last follow-up) in 58.1% (36/62), 42.3% (22/52), 30.5% (11/36), in TOFA, FILGO and UPA groups, respectively, (p &amp;lt;0.001). After IPTW, CFREM at W16 was higher in UPA (60.1%) compared to TOFA (38.9%) or FILGO groups (36.8%) (p &amp;lt; 0.001 for both). No predictor of efficacy/ failure was identified with these 3 JAK inhibitors. We failed to show any significant difference regarding clinical-endoscopic remission (UPA:16.5%, TOFA:16.5%, FILGO:12.8%) or HEMI (UPA:11.9%, TOFA: 4.4, FILGO: 12.7%). Among patients achieving CFREM at W16 (regardless of the dose), secondary loss of response (clinical relapse) was similar across the groups (TOFA:12.8%, FILGO: 19.2% and UPA: 10.3%; p = ns after IPTW). After adjustment, drug retention was longer for UPA compared to TOFA and FILGO groups (HR = 0.42 [0.21-0.85], p = 0.016) and shorter in FILGO than in TOFA group (HR = 1.60 [1.07-2.38], p = 0.021). No difference was demonstrated in terms of time to hospitalization or surgery between the 3 groups. Conclusion In this real-world evidence study, UPA was the most effective JAK inhibitor in UC at short and long-term but the large use of off-label maintenance doses in current practice needs further safety investigations.

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory disorder characterized by periods of relapse and remission. Current treatment options aim to achieve mucosal healing and sustain long-term remission, yet many patients experience treatment failure. Filgotinib (FIL), a selective JAK1 inhibitor, has emerged as a promising therapeutic agent in UC management with favorable outcomes in clinical trials. This study aimed to evaluate the real-world efficacy and safety of FIL in patients with moderate-to-severe UC. Methods We conducted a multicenter, observational, retrospective study involving adult patients with moderate-to-severe UC who were treated with FIL within the ENEIDA registry, a nationwide prospectively-maintained database. Data were collected from 28 Spanish IBD units between 12/2021 and 10/2024. Patients were eligible if they had an established diagnosis of UC, had been initiated on FIL and without previous colectomy. The primary outcome was clinical remission (partial Mayo ≤2 with no subscore &amp;gt;1 and no rectal bleeding) at week 12 and 52, along with its safety profile. Results A total of 91 patients were included (mean age of 37.5 years (SD 18), 63% male, and a median disease duration of 83 months [IQR, 35-148], 65% non-smokers, 15% extraintestinal manifestations). Most of them had extensive (49%) or left-sided colitis (42%). Prior exposure to anti-TNF was present in 89%, vedolizumab in 43%, and ustekinumab in 38%, with 18% also exposed to JAK inhibitors. The majority of patients had Mayo 2 or 3 endoscopic score (87%). All but 2 patients started FIL 200 mg bid (98%) and 27% received concomitant steroids or immunosuppressants (5%). Steroid-free clinical remission was 42% and 48% after 12 and 52 weeks, respectively (Figure 1). FIL persistence was 64% with median treatment duration of 6 months (IQR, 3.8-9.7). Those previously exposed to JAK inhibitors showed a 80% and 40% persistence after 12 and 52 weeks, respectively. This subgroup showed similar steroid-free clinical remission rates of 33% and 17%, respectively. Overall, hospital admission was indicated in 7% and colectomy in 1%. FIL was generally well-tolerated, with 18% of patients reporting at least one adverse event, 19% of them considered as serious, including herpes zoster infection in 2% (both vaccinated, 1 severe infection requiring FIL withdrawal), with no cardiovascular or thromboembolic events reported. Conclusion In this real-world, multicenter observational study, FIL demonstrated its efficacy in the induction and maintenance of clinical remission in patients with active UC. The real-world safety profile was consistent with previous data, with no unexpected adverse events. These findings support FIL as a valuable therapeutic option in the management of UC.

Abstract Background The addition of selective Janus kinase inhibitors (JAKi) –tofacitinib (TOFA), upadacitinib (UPA), and filgotinib (FILGO)– to the therapeutic arsenal for ulcerative colitis (UC) has provoked the need for comparative studies to establish their positioning in clinical practice. Aim: To compare the durability and the short- and long-term effectiveness of TOFA, UPA, and FILGO in UC, and to evaluate their real-world safety. Methods Adult patients who started JAKi treatment for UC (from April 2021) at least 8 weeks prior to data collection and were part of the prospectively maintained ENEIDA registry of GETECCU were included. Patients receiving concomitant biologic agents or with a history of colectomy were excluded. Patients were followed from the first JAKi dose until treatment discontinuation or their last visit. Effectiveness analysis was restricted to patients with active disease [Partial Mayo Score (PMS)&amp;gt;2] at JAKi initiation. Clinical effectiveness was measured using PMS, and concomitant steroid use was assessed at each visit. Patients who discontinued JAKi before their last visit were considered not in remission at subsequent time points (negative imputation). The propensity score was calculated using the inverse probability weighting (IPTW) method to balance confounding factors. Results A total of 611 patients were included (74 on FILGO, 369 on TOFA, and 168 on UPA). Baseline characteristics are summarised in Table 1. Discontinuation rates per patient-year were 57% for FILGO, 40% for TOFA, and 27% for UPA, with UPA showing significantly lower cumulative discontinuation rates compared to FILGO and TOFA (Fig. 1a). Reasons for discontinuation are detailed in Fig. 1b. Adjusted analysis indicated that baseline disease activity and prior JAKi exposure were associated with a higher discontinuation risk. Both TOFA and FILGO had significantly higher discontinuation risks than UPA. Steroid-free clinical remission (SFCR) rates during follow-up are shown in Fig. 2, with UPA demonstrating higher SFCR rates at most time points. At week 8, disease activity, prior JAKi exposure, and JAKi type were significantly associated with SFCR, with UPA having a higher probability of SFCR than both TOFA and FILGO (Table 2). The IPTW method confirmed all these results. Adverse events occurred in 12 (16%) patients with FILGO, 85 (23%) with TOFA, and 45 (27%) with UPA (p=0.2), with a minority leading to discontinuation (Fig. 1b). Conclusion In real-world practice, UPA shows superior effectiveness and drug survival compared to TOFA and FILGO in UC patients, with a comparable safety profile. These findings support the positioning of JAKi treatments in clinical practice and may guide treatment decisions in UC management.