Intestinal Research

Original Articles

Post-marketing surveillance of tofacitinib in patients with ulcerative colitis in Japan: a post hoc analysis of safety and effectiveness in older (≥65 years) and younger (<65 years) patients: Katsuyoshi Matsuoka, Takayuki Yamamoto, Minoru Matsuura, Toshimitsu Fujii, Shoko Arai, Yutaka Endo, Keiko Sato, Hirotoshi Yuasa, Yasushi Mizuno, Yuki Kobayashi, Tadakazu Hisamatsu; Received April 16, 2025 Accepted July 14, 2025 Published online November 10, 2025; DOI: https://doi.org/10.5217/ir.2025.00058 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
To assess, post hoc, tofacitinib safety/effectiveness in patients with ulcerative colitis (UC), stratified by age, using data from a 60-week post-marketing surveillance (PMS) study in Japan.
Methods
All patients with UC receiving tofacitinib in Japan were enrolled in a large PMS study. Incidence proportions of adverse events (AEs), incidence rates (IRs; unique patients with events/100 patient-years of exposure) of clinically important AEs, reasons for discontinuation, and partial Mayo score clinical remission, stratified by age ( ≥ 65 and < 65 years), were evaluated.
Results
The analysis included 212 older ( ≥ 65 years) and 1,770 younger ( < 65 years) patients. Demographics and baseline disease characteristics were generally similar between groups; however, more older versus younger patients had cardiovascular disease (23.1% vs. 4.6%). Incidence proportions of AEs were comparable between groups, but IRs (95% confidence intervals) in older versus younger patients were numerically higher for herpes zoster (9.81 [5.72–15.71] vs. 5.44 [4.28–6.82]), and higher for serious infections (4.45 [1.92–8.76] vs. 1.14 [0.65–1.85]). More older versus younger patients discontinued due to AEs (28.6% vs. 17.6%); more younger versus older patients discontinued due to insufficient clinical responses (50.3% vs. 35.2%). Clinical remission rates through 60 weeks were generally similar between groups.
Conclusions
Older patients had higher IRs of herpes zoster and serious infection than younger patients, although tofacitinib effectiveness was similar between age groups. Discontinuation due to AEs was more common in older patients. Despite the smaller sample size of older versus younger patients, a focused evaluation of older patients is of benefit.

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Efficacy and safety of etrasimod in Japanese patients with ulcerative colitis: results from a phase 2 dose-ranging study: Ken Takeuchi, Hiroshi Nakase, Tadakazu Hisamatsu, Katsuyoshi Matsuoka, Shoko Arai, Hirotoshi Yuasa, Motoki Oe, Ryosuke Ono, Michael Keating, Guibao Gu, Krisztina Lazin, Aoibhinn McDonnell, Koki Fukuta, Toshifumi Hibi; Received December 17, 2024 Accepted March 4, 2025 Published online April 25, 2025; DOI: https://doi.org/10.5217/ir.2024.00213 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). However, its efficacy, safety, and the appropriate dosage have not been extensively investigated in the Japanese population.
Methods
This phase 2, multicenter, randomized, double-blind, placebo-controlled dose-ranging, 12-week trial was carried out among Japanese patients with moderately to severely active UC. Patients were randomized 1:1:1 to receive etrasimod 1 mg once daily (QD), etrasimod 2 mg QD, or placebo. The primary efficacy endpoint was the proportion of patients achieving clinical remission at week 12. Secondary efficacy endpoints and treatmentemergent adverse events (TEAEs) were also investigated. Efficacy endpoints were presented as proportions of patients achieving each outcome.
Results
Overall, 17, 19, and 18 patients received etrasimod 1 mg QD, etrasimod 2 mg QD, and placebo, respectively. One patient receiving etrasimod 1 mg (6.7%), 5 patients receiving etrasimod 2 mg (26.3%), and no patients receiving placebo (0%) achieved clinical remission. More patients receiving etrasimod versus placebo achieved secondary endpoints, except endoscopic normalization, at week 12. TEAEs were experienced by 9 patients receiving etrasimod 1 mg (52.9%), 13 patients receiving etrasimod 2 mg (68.4%), and 10 patients receiving placebo (55.6%). None of the TEAEs were serious and none experienced by patients receiving etrasimod led to treatment discontinuation.
Conclusions
Overall, etrasimod 2 mg QD for up to 12 weeks appeared efficacious and safe in these Japanese patients with moderately to severely active UC. All TEAEs were mild to moderate in severity. (ClinicalTrials.gov: NCT05061446)

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Corrigenda and Errata

Corrigendum: Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies: Satoshi Motoya, Mamoru Watanabe, Hyo Jong Kim, Young Ho Kim, Dong Soo Han, Hirotoshi Yuasa, Junichi Tabira, Naoki Isogawa, Shoko Arai, Isao Kawaguchi, Toshifumi Hibi; Intest Res 2018;16(3):499-501. Published online July 27, 2018; DOI: https://doi.org/10.5217/ir.2018.16.3.499

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Citations

Citations to this article as recorded by

Post-inflammatory Abdominal Pain in Patients with Inflammatory Bowel Disease During Remission: A Comprehensive Review
Kazuya Takahashi, Iman Geelani Khwaja, Jocelyn Rachel Schreyer, David Bulmer, Madusha Peiris, Shuji Terai, Qasim Aziz
Crohn's & Colitis 360.2021;[Epub] CrossRef
Two cases in which tofacitinib effectively treated both ulcerative colitis and alopecia areata
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Original Article

IBD

Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies: Satoshi Motoya, Mamoru Watanabe, Hyo Jong Kim, Young Ho Kim, Dong Soo Han, Hirotoshi Yuasa, Junichi Tabira, Naoki Isogawa, Shoko Arai, Isao Kawaguchi, Toshifumi Hibi; Intest Res 2018;16(2):233-245. Published online April 30, 2018; DOI: https://doi.org/10.5217/ir.2018.16.2.233

Abstract PDF Supplementary Material PubReader ePub

<b>Background/Aims</b><br/>

Tofacitinib is an oral, small-molecule Janus kinase inhibitor being investigated for ulcerative colitis (UC). In OCTAVE Induction 1 and 2, patients with moderately to severely active UC received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks. Clinical responders in OCTAVE Induction were re-randomized to 52 weeks' therapy with placebo, tofacitinib 5 mg BID, or tofacitinib 10 mg BID.

Methods

We conducted post-hoc efficacy and safety analyses of East Asian patients in OCTAVE Induction 1 and 2 and OCTAVE Sustain.

Results

A total of 121 East Asian (Japan, Korea, and Taiwan) patients were randomized in OCTAVE Induction 1 and 2 (placebo, n=26; tofacitinib 10 mg BID, n=95), and 63 in OCTAVE Sustain (placebo, n=20; tofacitinib 5 mg BID, n=22; tofacitinib 10 mg BID, n=21). At week 8 of OCTAVE Induction 1 and 2, 18.9% of patients (18/95) achieved remission with tofacitinib 10 mg BID versus 3.8% (1/26) with placebo. In OCTAVE Sustain, the week 52 remission rates were 45.5% (10/22), 47.6% (10/21), and 15.0% (3/20) with 5 mg BID, 10 mg BID, and placebo, respectively. Adverse event rates were similar between groups in OCTAVE Induction and numerically higher with tofacitinib in OCTAVE Sustain. Serious adverse event rates were similar across groups in all studies. Infections were numerically more frequent with tofacitinib than placebo. Increases in serum lipid levels were observed with tofacitinib.

Conclusions

In East Asian patients with UC, tofacitinib demonstrated numerically greater efficacy versus placebo as induction and maintenance therapy, with a safety profile consistent with the global study population. ClinicalTrials.gov: NCT01465763; NCT01458951; NCT01458574.

Citations

Citations to this article as recorded by

Post-marketing surveillance of tofacitinib in patients with ulcerative colitis in Japan: a final report of safety and effectiveness data
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Journal of Gastroenterology.2025; 60(8): 979. CrossRef
Clinical Outcomes for Patients With Ulcerative Colitis in Cases of Withdrawal and Resumption of Janus Kinase Inhibitors: Multicenter Cohort Study
Yasuki Sano, Yuka Ito, Naoto Yagi, Yusuke Honzawa, Norimasa Fukata, Makoto Naganuma
Crohn's & Colitis 360.2025;[Epub] CrossRef
Real-life effectiveness and safety of tofacitinib treatment in patients with ulcerative colitis: a KASID multicenter cohort study
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Therapeutic Advances in Gastroenterology.2023;[Epub] CrossRef
Factors predicting clinical and endoscopic remission with placebo therapy in East Asian patients with ulcerative colitis: a systematic review and meta-analysis
Jian Zeng, Zhong Wang, Xiao-Jun Yang
European Journal of Clinical Pharmacology.2022; 78(7): 1069. CrossRef
Personalized medicine in inflammatory bowel disease: Perspectives on Asia
Su Hyun Park, Sang Hyoung Park
Journal of Gastroenterology and Hepatology.2022; 37(8): 1434. CrossRef
Safety and efficacy of long‐term tofacitinib treatment in East Asian patients with ulcerative colitis in OCTAVE Open
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