Hibi Toshifumi, Motoya Satoshi, Hisamatsu Tadakazu, Hirai Fumihito, Watanabe Kenji, Matsuoka Katsuyoshi, Saruta Masayuki, Kobayashi Taku, Feagan Brian G, Tasset Chantal, Besuyen Robin, Yun Chohee, Crans Gerald, Zhang Jie, Kondo Akira, Watanabe Mamoru
Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
Hokkaido Prefectural Welfare Federation of Agricultural Cooperatives, Sapporo-Kosei General Hospital, Sapporo, Japan.
Intest Res. 2023 Jan;21(1):110-125. doi: 10.5217/ir.2021.00143. Epub 2022 Mar 11.
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.
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.
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).
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.
背景/目的：在2b/3期SELECTION试验中，对日本溃疡性结肠炎（UC）患者评估了每日一次口服的Janus激酶1选择性抑制剂非戈替尼的安全性和疗效。
SELECTION（NCT02914522）是一项随机、安慰剂对照试验，包括2项诱导研究和1项维持研究。中度至重度活动性UC的成人患者在诱导研究A（未使用过生物制剂）或B（使用过生物制剂）中随机分组，接受非戈替尼200mg、100mg或安慰剂，每日一次，共11周。在第10周达到临床缓解或梅奥诊所评分有反应的患者进入47周的维持研究。对在日本入组的日本患者评估疗效和安全性结果。
总体而言，诱导研究A和B分别有37例和72例日本患者在日本入组，54例进入维持研究。在诱导研究A（4/15 [26.7%] 对0/6 [0%]）和维持研究（5/20 [25.0%] 对0/9 [0%]）中，接受非戈替尼200mg治疗达到临床缓解的患者比例在数值上高于接受安慰剂治疗的患者，但在诱导研究B中并非如此（1/29 [3.4%] 对1/14 [7.1%]）。两种剂量耐受性均良好，未发现新的安全信号。在诱导研究A（2.3%，1/44）和维持研究（5.0%，1/20）中，各有1例接受非戈替尼200mg治疗的患者报告发生带状疱疹。
这些数据以及整个SELECTION人群的数据表明，200mg非戈替尼对日本UC患者具有作为一种可行治疗选择的潜力。由于患者数量较少，数据应谨慎解读。
