Intest Res.  2023 Jan;21(1):110-125. 10.5217/ir.2021.00143.

Efficacy and safety of filgotinib as induction and maintenance therapy for Japanese patients with moderately to severely active ulcerative colitis: a post-hoc analysis of the phase 2b/3 SELECTION trial

• Hibi T
• Motoya S
• Hisamatsu T
• Hirai F
• Watanabe K
• Matsuoka K
• Saruta M
• Kobayashi T
• Feagan BG
• Tasset C
• Besuyen R
• Yun C
• Crans G
• Zhang J
• Kondo A
• Watanabe M

• KMID: 2539010
• DOI: http://doi.org/10.5217/ir.2021.00143

Abstract

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.

Keyword

Colitis, ulcerative; Filgotinib; Janus kinase inhibitors; Japan

Figure

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  Fig. 1. Proportion of Japanese patients achieving clinical remission (A, B), MCS remission (C, D), MCS remission (alternative definition) (E, F), endoscopic remission (G, H), and histologic remission (I, J) in induction studies A and B at week 10. Error bars indicate 95% confidence intervals (CIs). CIs for 0-responder treatment arms are not presented. CIs for treatment differences between 0-responder treatment arms are not presented. 95% CIs were calculated based on normal approximation with a continuity correction. Clinical remission was defined as an MES of 0 or 1, rectal bleeding subscore of 0, and at least a 1-point decrease in stool frequency from induction baseline to achieve a subscore of 0 or 1. MCS remission was defined as a total MCS of not more than 2 and no single subscore greater than 1. MCS remission (alternative definition) was defined as rectal bleeding, stool frequency, and physician’s global assessment subscores of 0; an endoscopic subscore of 0 or 1; and an overall MCS of 1 or 0. Endoscopic remission was defined as an MES of 0. Histologic remission was defined as grade 0 Geboes score of ≤0.3, grade 1 score of ≤1.1, grade 2A score of ≤2A.3, grade 2B score of 2B.0, grade 3 score of 3.0, grade 4 score of 4.0, and grade 5 score of 5.0. MCS, Mayo Clinic score; MES, Mayo endoscopic subscore.

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  Fig. 2. Proportion of Japanese patients achieving clinical remission (A), 6-month corticosteroid-free clinical remission (B), sustained clinical remission (C), MCS remission (D), MCS remission (alternative definition) (E), endoscopic remission (F), and histologic remission (G) in the maintenance study at week 58. Separate comparisons were conducted between the filgotinib 200 mg group and the respective placebo group, and the filgotinib 100 mg group and the respective placebo group in the maintenance study. Error bars indicate 95% confidence intervals (CIs). CIs for 0-responder treatment arms are not presented. CIs for treatment differences between 0-responder treatment arms are not presented. 95% CIs were calculated based on normal approximation with a continuity correction. Clinical remission was defined as an MES of 0 or 1, rectal bleeding subscore of 0, and at least a 1-point decrease in stool frequency from induction baseline to achieve a subscore of 0 or 1. Six-month corticosteroid-free clinical remission was defined as clinical remission with no corticosteroid use for the indication of UC for at least 6 months before week 58 among patients who were receiving corticosteroids at the baseline of the maintenance study. Sustained clinical remission was defined as clinical remission at both week 10 and week 58. MCS remission was defined as a total MCS of not more than 2 and no single subscore greater than 1. MCS remission (alternative definition) was defined as rectal bleeding, stool frequency, and physician’s global assessment subscores of 0; an endoscopic subscore of 0 or 1; and an overall MCS of 1 or 0. Endoscopic remission was defined as an MES of 0. Histologic remission was defined as grade 0 Geboes score of ≤0.3, grade 1 score of ≤1.1, grade 2A score of ≤2A.3, grade 2B score of 2B.0, grade 3 score of 3.0, grade 4 score of 4.0, and grade 5 score of 5.0. aOnly patients who received corticosteroids before enrollment were included. MCS, Mayo Clinic score; MES, Mayo endoscopic subscore; UC, ulcerative colitis.

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