Background/Aims To evaluate the efficacy and safety of upadacitinib in patients with highly refractory pediatric-onset inflammatory bowel disease (IBD) and to describe the outcomes of upadacitinib-vedolizumab combination therapy (UVCT) in treatment-refractory cases.
Methods This retrospective, single-center study included 18 patients (7 with ulcerative colitis, 6 with Crohn’s disease, and 5 with very early-onset IBD) who received upadacitinib between November 2022 and November 2025. Five patients underwent UVCT. All patients had previously failed multiple therapies (median, 3 prior advanced therapies). The primary outcome was the upadacitinib continuation rate. The secondary outcomes included corticosteroid- and tacrolimusfree remission rates, safety profiles, and UVCT outcomes.
Results The median age at upadacitinib initiation was 13.0 years (range, 2.3–21.6 years). The 52-week continuation rate was 55.6%. Among patients who received corticosteroids at baseline, 50% achieved corticosteroid-free status by 6 months; all patients who received tacrolimus at baseline discontinued tacrolimus within 6 months. No serious adverse events attributable to upadacitinib were observed and no cases of herpes zoster reactivation occurred. Five patients with persistent corticosteroid/tacrolimus dependence underwent UVCT, 4 of whom achieved clinical remission with withdrawal of corticosteroids/tacrolimus, with endoscopic improvement confirmed in 3. One patient with very early-onset IBD required colectomy.
Conclusions Upadacitinib demonstrated acceptable efficacy and safety in patients with highly refractory pediatric-onset IBD. In this small subgroup, UVCT was associated with clinical remission in most patients (4/5), suggesting that it may warrant further investigation as a salvage strategy to avert surgery. Prospective, multicenter studies are needed to define the optimal positioning within pediatric-onset IBD treatment algorithms.
Background/Aims There is a paucity of data regarding the comparative safety of Janus kinase inhibitors (JAKi) compared to biologic therapy in inflammatory bowel disease (IBD).
Methods A retrospective cohort study was conducted using the U.S. Collaborative Network to assess the risk of adverse events in patients with IBD on JAKi compared to biologic therapies (tumor necrosis factor inhibitor, ustekinumab or vedolizumab). Outcomes assessed included infections, major adverse cardiovascular events (MACE), malignancy, venous thromboembolism (VTE), gastrointestinal perforations and laboratory abnormalities within 2 years. 1:1 propensity score matching (PSM) was performed.
Results There were 3,186 patients in the JAKi cohort (mean age 44.3 ± 17.1, 46.5% male sex, 85.7% ulcerative colitis, 72% tofacitinib) and 60,462 patients in the biologic cohort. After PSM, there was no difference in the risk of bacterial (adjusted odds ratio [aOR], 1.08; 95% confidence interval [CI], 0.82–1.43), viral (aOR, 1.06; 95% CI, 0.84–1.32), or fungal infections (aOR, 1.10; 95% CI, 0.84–1.44), MACE (aOR, 0.72; 95% CI, 0.47–1.10), malignancy (aOR, 0.98; 95% CI, 0.71–1.35), and VTE (aOR, 0.95; 95% CI, 0.67–1.34). This was consistent in subgroup analyses based on IBD type, JAKi type and age group. There was a higher risk of low-density lipoprotein ≥ 190 mg/dL (aOR, 1.78; 95% CI, 1.03–3.05) and grade 3 or higher lymphopenia (aOR, 2.28; 95% CI, 1.60–3.26) in the JAKi cohort. There was no difference in the 4-year risk of MACE or malignancy in the tofacitinib cohort compared with the biologic cohort.
Conclusions Our real-world study did not show an increased risk of adverse events except severely elevated LDL and lymphopenia in patients on JAKi compared to biologic therapy.
Background/Aims This post hoc analysis of the phase 2b/3 SELECTION (NCT02914522) study and its long-term extension (SELECTIONLTE; NCT02914535) evaluated the impact of filgotinib 200 mg (FIL200) on health-related quality of life (HRQoL) and work productivity in Japanese patients with ulcerative colitis over 3 years.
Methods Patients in SELECTION were randomized to FIL200, filgotinib 100 mg, or placebo (PBO) during the induction phase. Week-10 responders were re-randomized to continue assigned treatment or PBO in the 47-week maintenance phase. Patients who completed the SELECTION induction and maintenance phases (completers) and week-10 non-responders could enter SELECTIONLTE. HRQoL and work productivity were assessed using EQ 5-dimension (EQ-5D), EQ visual analog scale, Inflammatory Bowel Disease Questionnaire (IBDQ), 36-item Short Form Health Survey (SF-36), and Work Productivity and Activity Impairment (WPAI) questionnaires at week 10 (FIL200 vs. PBO), and at week 10 and years 1–3 (completers and non-responders who received only FIL200 in SELECTION+SELECTIONLTE).
Results Proportions of patients with minimal clinically important differences (MCIDs) at week 10 were higher with FIL200 versus PBO for IBDQ total score (77% vs. 54%), SF-36 mental component summary (58% vs. 21%), and SF-36 physical component summary (54% vs. 36%). All measures (except WPAI absenteeism) showed mean score changes from baseline at week 10 in the direction of improved HRQoL with FIL200 versus PBO. MCID rates were maintained in completers up to 3 years and increased notably in non-responders (except WPAI absenteeism and EQ-5D) from week 10 to years 1–3.
Conclusions FIL200 treatment was associated with sustained improvements in HRQoL and work productivity over 3 years in Japanese patients with ulcerative colitis, consistent with the overall SELECTION and SELECTIONLTE trial populations.
Seung Min Hong, Dong Hyun Kim, June Hwa Bae, Seung Yong Shin, Eun Mi Song, Ji Eun Kim, Young Joo Yang, Jiyoung Yoon, Sang-Bum Kang, Eun Soo Kim, Seong-Eun Kim, Seong-Jung Kim, Jun Lee, Soo-Young Na, Soo Jung Park, Sang Hyoung Park, Miyoung Choi, Myung Ha Kim, Won Moon, Sung-Ae Jung, KASID Guidelines Taskforce Team of the Korean Association for the Study of Intestinal Diseases (KASID)
Intest Res 2026;24(1):27-37. Published online January 28, 2026
Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.
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Treatment persistence after switching between anti-tumor necrosis factor agents and tofacitinib in ulcerative colitis: A nationwide claims-based cohort study in South Korea Ji Eun Baek, Arum Choi, Han Hee Lee, Bo-In Lee, Kang-Moon Lee Therapeutic Advances in Gastroenterology.2026;[Epub] CrossRef
Inflammatory bowel disease is increasingly recognized as a significant clinical entity in India, reflecting the country’s ongoing epidemiological transition. With a rising incidence and an expanding disease spectrum, the limitations of conventional therapeutic agents, such as corticosteroids and thiopurines, have become increasingly evident. This review examines the transformative role of Janus kinase inhibitors, particularly tofacitinib, in redefining therapeutic goals and bridging the gap between medical innovation and real-world implementation in resource-limited settings. Tofacitinib represents a pivotal advancement in the therapeutic landscape of ulcerative colitis (UC) in India, offering the advantages of oral administration, rapid onset of action, predictable pharmacokinetics, and cost-effective generic formulations–thereby overcoming several longstanding barriers to the adoption of advanced therapies. Accumulating real-world evidence from India supports its clinical utility across various phenotypes of UC, including corticosteroid-dependent or refractory disease, acute severe UC, ulcerative proctitis, elderly-onset UC, and in achieving deeper remission endpoints such as histologic healing. Furthermore, its incorporation into routine clinical practice has contributed to a measurable reduction in corticosteroid reliance, thereby aligning treatment strategies with international standards of care. By combining efficacy, safety, accessibility, and ease of use, tofacitinib has catalyzed a paradigm shift in the management of UC in the Indian context.
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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.
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Early Symptomatic Improvement Is Informing Long-Term Quality-of-Life Outcomes with Filgotinib Treatment in Ulcerative Colitis: A Post Hoc Analysis of the SELECTION and SELECTIONLTE Trials Fumihito Hirai, Christine Rudolph, Toshihiko Kaise, Toshifumi Hibi Inflammatory Intestinal Diseases.2026; 11(1): 270. CrossRef
In real-world clinical practice, 3 Janus kinase (JAK) inhibitors—tofacitinib, filgotinib, and upadacitinib—are now available for the treatment of ulcerative colitis. Emerging real-world evidence highlights distinct efficacy and safety profiles among these agents, largely attributed to differences in JAK selectivity and dosing strategies. Notably, data are accumulating on differential efficacy, predictors of therapeutic response, and outcomes in patients who switch between JAK inhibitors, contributing to a clearer understanding of the optimal positioning of each agent. Regarding safety, particular attention has been given to risks such as herpes zoster infection and drug-induced acne, underscoring the importance of appropriate patient education and individualized risk assessment. This review summarizes clinical trials and current real-world data on tofacitinib, filgotinib, and upadacitinib in ulcerative colitis, and discusses strategies for optimizing their clinical application.
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Background/Aims Filgotinib is an oral, once-daily, Janus kinase 1 preferential inhibitor approved for the treatment of ulcerative colitis (UC). This study aimed to assess symptomatic response with filgotinib 200 mg (FIL200) according to disease severity using baseline partial Mayo Clinic Score (pMCS).
Methods In the phase 2b/3 SELECTION study (NCT02914522), adults with moderate-to-severe UC were randomized to receive FIL200, filgotinib 100 mg, or placebo for 11 weeks in induction studies A (biologic-naive) and B (biologic-experienced). In this post hoc analysis, symptomatic remission (Mayo rectal bleeding subscore of 0 and stool frequency subscore ≤ 1) rates were assessed daily from baseline to day 15 and fortnightly from week 2 to week 10 by baseline pMCS (pMCS ≥ 7, pMCS < 7) in patients who received induction FIL200.
Results Of those who received FIL200 in induction studies A and B, 90 and 148 patients had a pMCS ≥ 7, and 155 and 114 had a pMCS < 7, respectively. Symptomatic remission rates were generally significantly higher in the pMCS < 7 than ≥ 7 group from day 2–15 (day 2: 8.4% vs. 1.1%, P= 0.009 [induction study A]; 8.8% vs. 0.7%, P= 0.004 [induction study B]). However, by week 10, there was no longer a significant difference in the rates between the pMCS ≥ 7 and < 7 groups (43.3% vs. 54.8%, P= 0.124 [induction study A]; 26.4% vs. 39.5%, P= 0.099 [induction study B]).
Conclusions Symptomatic response to FIL200 occurred more rapidly in the less severe disease groups than in the more severe disease groups; however, regardless of disease severity, both groups benefited from continued FIL200 treatment.
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Robert Gilmore, Richard Fernandes, Imogen Hartley, Arteen Arzivian, Rupert Leong, Bridgette Andrew, Abhinav Vasudevan, Tessa Greeve, Gregory Thomas Moore, Steven Kim, Daniel Lightowler, Abhey Singh, Gillian Mahy, Aditya Mithanthaya, Kannan Venugopaul, Sangwoo Han, Robert Bryant, Jack West, Jonathan Segal, Britt Christensen, Crispin Corte, Nik Ding, Yoon-Kyo An, Jakob Begun
Intest Res 2025;23(3):347-357. Published online December 20, 2024
Background/Aims Upadacitinib is a novel selective Janus kinase inhibitor approved for use in ulcerative colitis. Clinical trials had rigorous criteria and excluded many patient subgroups. Given limited real-world effectiveness data, we examined outcomes of patients treated with upadacitinib for ulcerative colitis in a real-world population.
Methods Patients that commenced upadacitinib for moderate-to-severe ulcerative colitis from September 2022 until March 2023 were identified at 13 inflammatory bowel disease centers across Australia. Clinical, biochemical, endoscopic, and intestinal ultrasound outcomes were recorded retrospectively at baseline, week 8, and week 16.
Results One hundred and fifty-two patients (61 female [40%], median age 38 years [interquartile range, 28–50]) were included. The primary endpoint of clinical remission was met in 79% at week 8, and 84% at week 16. A total of 42 patients (28%) with prior tofacitinib exposure were included. No significant difference in clinical remission was observed by week 16 between tofacitinib experienced compared to tofacitinib naïve patients (86% vs. 84%, P= 0.67). Complete intestinal ultrasound data was available for 36 patients, showing transmural remission in 64% at week 8 and 81% at week 16, with a decrease in median bowel wall thickness of 2.3 mm and 2.4 mm, respectively.
Conclusions Upadacitinib resulted in high rates of clinical remission at 8 and 16 weeks in this large real-world cohort of ulcerative colitis patients. Upadacitinib is effective in patients with prior tofacitinib exposure. Intestinal ultrasound shows significant rates of transmural remission at week 8, sustained through week 16.
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Background/Aims The safety and efficacy of filgotinib, a once-daily oral Janus kinase 1 preferential inhibitor, were evaluated in Japanese patients with ulcerative colitis (UC) in the phase 2b/3 SELECTION trial.
Methods SELECTION (NCT02914522) was a randomized, placebo-controlled trial comprising 2 induction studies and a maintenance study. Adults with moderately to severely active UC were randomized in induction study A (biologic-naïve) or B (biologic-experienced) to receive filgotinib 200 mg, 100 mg, or placebo once daily for 11 weeks. Patients in clinical remission or Mayo Clinic score response at week 10 entered the 47-week maintenance study. Efficacy and safety outcomes were assessed in Japanese patients enrolled in Japan.
Results Overall, 37 and 72 Japanese patients were enrolled in Japan in induction studies A and B, respectively, and 54 entered the maintenance study. Numerically higher proportions of filgotinib 200 mg-treated than placebo-treated patients achieved clinical remission in induction study A (4/15 [26.7%] vs. 0/6 [0%]) and the maintenance study (5/20 [25.0%] vs. 0/9 [0%]), but not induction study B (1/29 [3.4%] vs. 1/14 [7.1%]). Both doses were well tolerated, and no new safety signals were noted. Herpes zoster was reported in 1 filgotinib 200 mg-treated patient in each of induction study A (2.3%, 1/44) and the maintenance study (5.0%, 1/20).
Conclusions These data, alongside those of the overall SELECTION population, suggest the potential of filgotinib 200 mg as a viable treatment option for Japanese patients with UC. Owing to small patient numbers, data should be interpreted cautiously.
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