Comparative Efficacy and Safety of Three Janus Kinase Inhibitors in Ulcerative Colitis: A Real-World Multicentre Study in Japan

Shintaro Akiyama; Hiromichi Shimizu; Akiko Tamura; Kaoru Yokoyama; Toshiyuki Sakurai; Mariko Kobayashi; Makoto Eizuka; Shunichi Yanai; Kei Nomura; Tomoyoshi Shibuya; Masahiro Takahara; Sakiko Hiraoka; Minako Sako; Atsushi Yoshida; Kozo Tsuruta; Shinichiro Yoshioka; Miki Koroku; Teppei Omori; Masayuki Saruta; Takayuki Matsumoto; Ryuichi Okamoto; Kiichiro Tsuchiya; Toshimitsu Fujii

doi:10.1111/apt.18406

Comparative Efficacy and Safety of Three Janus Kinase Inhibitors in Ulcerative Colitis: A Real-World Multicentre Study in Japan

Aliment Pharmacol Ther. 2024 Nov 22. doi: 10.1111/apt.18406. Online ahead of print.

Authors

Shintaro Akiyama¹, Hiromichi Shimizu², Akiko Tamura², Kaoru Yokoyama³, Toshiyuki Sakurai⁴, Mariko Kobayashi¹, Makoto Eizuka⁵, Shunichi Yanai⁵, Kei Nomura⁶, Tomoyoshi Shibuya⁶, Masahiro Takahara⁷, Sakiko Hiraoka⁷, Minako Sako⁸, Atsushi Yoshida⁹, Kozo Tsuruta¹⁰, Shinichiro Yoshioka¹⁰, Miki Koroku¹¹, Teppei Omori¹¹, Masayuki Saruta⁴, Takayuki Matsumoto⁵, Ryuichi Okamoto², Kiichiro Tsuchiya¹, Toshimitsu Fujii²

Affiliations

¹ Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.
² Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Bunkyo-ku, Tokyo, Japan.
³ Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, Japan.
⁴ Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
⁵ Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Yahaba, Japan.
⁶ Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
⁷ Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁸ Center for Inflammatory Bowel Disease, Tokyo Yamate Medical Center, Japan Community Healthcare Organization, Tokyo, Japan.
⁹ Center for Gastroenterology and Inflammatory Bowel Disease, Ofuna Chuo Hospital, Kamakura, Japan.
¹⁰ Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
¹¹ Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.

PMID: 39578704
DOI: 10.1111/apt.18406

Abstract

Background: Three Janus kinase (JAK) inhibitors are approved for ulcerative colitis (UC) in Japan.

Aim: To compare the real-world efficacy and safety of these three JAK inhibitors in UC.

Methods: This was a multicentre, retrospective study of patients with UC started on JAK inhibitors. The primary outcome was clinical remission at 10, 26 and 58 weeks, and at the most recent follow-up. To compare the efficacy and safety among the JAK inhibitors, we created three matched cohorts (upadacitinib vs. filgotinib, tofacitinib vs. filgotinib and upadacitinib vs. tofacitinib) using propensity score matching.

Results: We identified 228 upadacitinib-treated patients (median follow-up 49 weeks; IQR 25-72), 215 filgotinib-treated patients (follow-up 56 weeks; IQR 17-82) and 159 tofacitinib-treated patients (follow-up 112 weeks; IQR 10-258). Clinical remission rates for upadacitinib, filgotinib and tofacitinib at the most recent follow-up were 72.8%, 50.6% and 45.8%, respectively. Over 70% of the patients previously treated with other biologics or JAK inhibitors achieved clinical remission with upadacitinib. On multivariate analysis, the number of previous advanced therapies was inversely associated with the efficacy of filgotinib and tofacitinib. Comparative analysis showed that upadacitinib-treated patients had higher efficacy and lower risk of discontinuation than patients treated with other JAK inhibitors. However, upadacitinib had a significant risk of acne.

Conclusions: Considering the particularly high efficacy of upadacitinib, even in patients with refractory UC, filgotinib or tofacitinib may be considered as an upfront JAK inhibitor before using upadacitinib.

Keywords: Janus kinase; filgotinib; tofacitinib; ulcerative colitis; upadacitinib.