Yasuo Suzuki1, Mamoru Watanabe2, Toshiyuki Matsui3, Satoshi Motoya4, Tadakazu Hisamatsu5, Hirotoshi Yuasa6, Junichi Tabira6, Naoki Isogawa6, Shinichi Tsuchiwata6, Shoko Arai7, Toshifumi Hibi8. 1. Toho University, Sakura Medical Center, Sakura, Japan. 2. TMDU Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. 3. Department of Gastroenterology, Fukuoka University, Chikushi Hospital, Fukuoka, Japan. 4. IBD Center, Sapporo Kosei Hospital, Sapporo, Japan. 5. Third Department of Internal Medicine, Kyorin University, Mitaka, Japan. 6. Global Product Development - JPN, Pfizer Japan Inc., Tokyo, Japan. 7. Pfizer Innovative Health - JPN, Pfizer Japan Inc., Tokyo, Japan. 8. Center for Inflammatory Bowel Disease, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan.
Abstract
BACKGROUND: Tofacitinib is an oral, small molecule Janus kinase inhibitor approved in Japan for the treatment of ulcerative colitis (UC). Differences in the safety profile of tofacitinib in Japanese patients versus the global population, such as a higher risk of herpes zoster, have been reported. OBJECTIVES: We conducted post hoc analyses of tofacitinib treatment in Japanese patients with moderate-to-severe UC in two global phase III studies. METHODS: In OCTAVE Induction 1 (NCT01465763), 62 patients were randomized to placebo or tofacitinib 10 mg twice daily (b.i.d.). In OCTAVE Sustain (NCT01458574), 39 patients with clinical response in OCTAVE Induction 1 were re-randomized to placebo, tofacitinib 5 mg, or 10 mg b.i.d. Efficacy endpoints included: remission (primary endpoint; total Mayo score ≤2; no individual subscore >1; rectal bleeding subscore 0); mucosal healing (Mayo endoscopic subscore ≤1); clinical response (≥30% and ≥3-point decrease from induction study baseline total Mayo score; decrease in rectal bleeding subscore ≥1 or absolute subscore ≤1). Adverse events (AEs) and clinical laboratory parameters were recorded. RESULTS: At week 8 of OCTAVE Induction 1, 22.4% of patients achieved remission with tofacitinib (placebo, 7.7%). At week 52 of OCTAVE Sustain, 31.3% and 66.7% of patients receiving tofacitinib 5 and 10 mg b.i.d., respectively, achieved remission (placebo, 9.1%). The occurrence of AEs or serious AEs in Japanese patients was generally similar to that in the global study population, with no new or unexpected safety risks observed. CONCLUSIONS: Although patient numbers were small, tofacitinib demonstrated numerically greater efficacy versus placebo among Japanese patients in OCTAVE Induction 1 and OCTAVE Sustain, with a safety profile consistent with that of the global study population.
BACKGROUND: Tofacitinib is an oral, small molecule Janus kinase inhibitor approved in Japan for the treatment of ulcerative colitis (UC). Differences in the safety profile of tofacitinib in Japanese patients versus the global population, such as a higher risk of herpes zoster, have been reported. OBJECTIVES: We conducted post hoc analyses of tofacitinib treatment in Japanese patients with moderate-to-severe UC in two global phase III studies. METHODS: In OCTAVE Induction 1 (NCT01465763), 62 patients were randomized to placebo or tofacitinib 10 mg twice daily (b.i.d.). In OCTAVE Sustain (NCT01458574), 39 patients with clinical response in OCTAVE Induction 1 were re-randomized to placebo, tofacitinib 5 mg, or 10 mg b.i.d. Efficacy endpoints included: remission (primary endpoint; total Mayo score ≤2; no individual subscore >1; rectal bleeding subscore 0); mucosal healing (Mayo endoscopic subscore ≤1); clinical response (≥30% and ≥3-point decrease from induction study baseline total Mayo score; decrease in rectal bleeding subscore ≥1 or absolute subscore ≤1). Adverse events (AEs) and clinical laboratory parameters were recorded. RESULTS: At week 8 of OCTAVE Induction 1, 22.4% of patients achieved remission with tofacitinib (placebo, 7.7%). At week 52 of OCTAVE Sustain, 31.3% and 66.7% of patients receiving tofacitinib 5 and 10 mg b.i.d., respectively, achieved remission (placebo, 9.1%). The occurrence of AEs or serious AEs in Japanese patients was generally similar to that in the global study population, with no new or unexpected safety risks observed. CONCLUSIONS: Although patient numbers were small, tofacitinib demonstrated numerically greater efficacy versus placebo among Japanese patients in OCTAVE Induction 1 and OCTAVE Sustain, with a safety profile consistent with that of the global study population.
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