Efficacy and safety of ustekinumab in Japanese patients with moderately to severely active Crohn's disease: a subpopulation analysis of phase 3 induction and maintenance studies

Abstract

Background/aims: Efficacy and safety of ustekinumab were evaluated in a Japanese subpopulation with moderately to severely active Crohn's disease (CD) in UNITI-1, UNITI-2 and IM-UNITI studies and results were compared with the overall population.

Methods: Overall, patients in UNITI-1 (Japan, n=56; failed response to tumor necrosis factor antagonist) and UNITI-2 (Japan, n=26; failed response to prior conventional therapy) were randomized to placebo or ustekinumab intravenous induction (130 mg or ~6 mg/kg) at week 0. Responders to ustekinumab induction therapy (Japan, n=21) were randomized to placebo or ustekinumab (90 mg, subcutaneous) maintenance (every 12 weeks [q12w] or 8 weeks [q8w]) in IM-UNITI. The primary endpoint was clinical response at week 6 for induction studies and clinical remission at week 44 for maintenance study.

Results: Percentage of patients achieving clinical response at week 6 was greater in ustekinumab 130 mg and ~6 mg/kg groups than in the placebo group (UNITI-1: 36.8% and 31.6% vs. 27.8%, respectively, for Japanese; 34.3% and 33.7% vs. 21.5%, respectively, for overall; UNITI-2: 37.5% and 55.6% vs. 11.1%, respectively, for Japanese; 51.7% and 55.5% vs. 28.7%, respectively, for overall). Clinical remission rate at week 44 during maintenance was greater in the ustekinumab 90 mg SC q12w and q8w groups than in the placebo group (50.0% and 55.6% vs. 25.0%, respectively, for Japanese; 48.8% and 53.1% vs. 35.9%, respectively, for overall). Efficacy and safety results observed in the Japanese subpopulation were generally consistent with those in the overall population.

Conclusions: Ustekinumab could be considered as a new therapeutic option for moderately to severely active CD in Japanese patients. Both ustekinumab induction and maintenance treatments were generally well tolerated (Clinical Trial Registration: NCT01369329, NCT01369342, NCT01369355).

Keywords: Crohn disease; Interleukin-12/23; Japan; Ustekinumab.

Conflict of interest statement

Conflict of interest: Yuya Imai, Yoko Murata, Nobuko Matsushima, and Richuan Zheng are employees of Janssen Pharmaceutical K.K., Japan. Dr. Christopher Gasink is an employee of Janssen Research & Development, LLC, United States. Dr. Toshifumi Hibi is a consultant for Janssen Pharmaceutical K.K., Japan.

Figures

Fig. 1. Study design of phase 3 CD program for ustekinumab. Patients randomized to placebo and patients who were nonresponders to ustekinumab were eligible for nonrandomized maintenance dose after completion of induction study. aWeight range based ustekinumab doses approximating at 6 mg/kg; bIf there was no clinical response achieved at week 8, the study treatment was discontinued. TNF, tumor necrosis factor; IV, intravenous; q8w, every 8 weeks; q12w, every 12 weeks. Adapted from Feagan BG, et al. N Engl J Med 2016;375:1946-1960.19

Fig. 2. Primary endpoint in the overall study population and Japanese subpopulation. The primary efficacy outcome in induction and maintenance studies observed in Japanese subpopulation were similar to the global study population. aP<0.001 vs. placebo; bP<0.01 vs. placebo; cP=0.04. q8w, every 8 weeks; q12w, every 12 weeks.

Fig. 3. Median change in CDAI scores over time. In the induction studies and maintenance study, the median change in CDAI scores consistently improved with ustekinumab compared with that with placebo in the Japanese subpopulation and overall study population. All P<0.05 vs. placebo in the overall population of the UNITI-1, UNITI-2, and IM-UNITI studies. q12w, every 12 weeks; q8w, every 8 weeks. Panel B, D, and F are adapted from Feagan BG, et al. N Engl J Med 2016;375:1946-1960, with permission Massachusetts Medical Society.