Introduction

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.

Aims & 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 32 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 (defined as partial Mayo ≤2 with no subscore >1 and no rectal bleeding) at week 12 and 52, along with its safety profile.

Results

A total of 100 patients were included (mean age of 38.1 years (SD 18), 58% male, and a median disease duration of 98 months [IQR, 37-166], 61% non-smokers, 18% extraintestinal manifestations). Most of them had extensive (51%) or left-sided colitis (40%). Prior exposure to anti-TNF was present in 81%, vedolizumab in 42%, and ustekinumab in 34%, with 18% also exposed to JAK inhibitors; including 27% exposed to >2 mechanisms. The majority of patients had Mayo 2 or 3 endoscopic score at baseline (88%). All but 2 patients started FIL 200 mg bid (98%) and 30% received concomitant steroids or immunosuppressants (4%).
Steroid-free clinical remission was 43% and 32% after 12 and 52 weeks, respectively. FIL persistence was 62% with median treatment duration of 7 months (IQR, 4-11). Among those previously exposed to JAK inhibitors, persistence was 83% and 39% after 12 and 52 weeks, respectively. This subgroup showed steroid-free clinical remission rates of 33% and 14%, respectively. Overall, hospital admission was indicated in 6% and colectomy in 1%.
FIL was generally well-tolerated, with 17% of patients reporting at least one adverse event, 18% 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.

Disclosure

IRL has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Alfasigma, Biogen, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Johnson & Johnson, Eli Lilly, Mirum Pharmaceuticals, Merck, Pfizer, Roche, Takeda, and Tillotts Pharma. Research support from AbbVie. IRL is supported by a research grant from Gobierno Vasco-Eusko Jaurlaritza [Grant No 2020111061 and 2023222006].

Introduction

We conducted a retrospective analysis of a large U.S. based administrative claims database comparing the risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) among patients with inflammatory bowel disease (IBD) initiating advanced biological therapies.

Aims & Methods

Patients with CD and UC who were incident users of advanced biological agents from 2013 to 2023 were identified within the Optum Labs® database. The therapeutic agents included either tumor necrosis factor-α (TNF) antagonists (infliximab, adalimumab, and certolizumab pegol), IL-12/23 antagonists (ustekinumab), IL-23 antagonists (risankizumab), anti-integrin agents (vedolizumab), Janus kinase (JAK) inhibitors (tofacitinib and upadacitinib), or S1PR modulators (ozanimod). Eligible patients were required to have continuous insurance coverage for at least one year before and after treatment initiation. We estimated incidence rates (IRs) and compared risks for VTE and MACE (myocardial infarction and stroke). Fatal cardiovascular outcomes were excluded due to limited specificity and data constraints.
To account for baseline confounding, we applied stabilized inverse probability of treatment weighting (IPTW) using multinomial propensity scores. Hazard ratios were estimated using Cox proportional hazard models.

Results

We included 12,245 patients with CD (mean age: 44.5 ± 17.5 years; 54.2% female; 30.9% using concomitant steroids), and 9,430 patients with UC (mean age: 47.5 ± 17.7 years; 49.2% female; 50% on concomitant corticosteroids). Patients receiving JAK inhibitors and vedolizumab were more likely to have higher comorbidity burden than others for CD while those receiving IL-23 antagonists had the most comorbid burden for UC patients, when assessed through proportion of patients with Charlson comorbidity index of ≥ 5. In UC patients, VTE incidence rates ranged from 1.69 to 2.01 for VTE and MACE rates from 0.52 to 0.99 per 100 person-years. For CD, VTE incidence rates ranged from 0.89 to 2.33 and for MACE, 0.68 to 1.73. Hazard ratios comparing the risk of events across therapies is presented in table 1.

Table 1: Hazard ratios for risk of VTE and MACE in patients with Crohn’s disease and Ulcerative colitis receiving advanced biological therapies and small molecules

Conclusion

In this large real-world IBD cohort, there was no difference in risk of adverse cardiovascular and thrombotic events between any biological agent or small molecule, in compairosn to TNF antagnoists.

Disclosure

• CM: Consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Forte Biosciences, Fresenius Kabi, Gilead, Janssen, McKesson, Mirador Therapeutics, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Eli Lilly, Ferring, Pfizer.
• VJ: Consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome,Takeda, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi
• SS: Research grants from Pfizer