Efficacy and safety of upadacitinib in Japanese patients with rheumatoid arthritis (SELECT-SUNRISE): a placebo-controlled phase IIb/III study

Hideto Kameda, Tsutomu Takeuchi, Kunihiro Yamaoka, Motohiro Oribe, Mitsuhiro Kawano, Yijie Zhou, Ahmed A Othman, Aileen L Pangan, Susumu Kitamura, Sebastian Meerwein, Yoshiya Tanaka, Hideto Kameda, Tsutomu Takeuchi, Kunihiro Yamaoka, Motohiro Oribe, Mitsuhiro Kawano, Yijie Zhou, Ahmed A Othman, Aileen L Pangan, Susumu Kitamura, Sebastian Meerwein, Yoshiya Tanaka

Abstract

Objective: To evaluate upadacitinib efficacy and safety dose response in Japanese patients with active RA and an inadequate response to conventional synthetic DMARDs (csDMARDs).

Methods: This was a multicentre, phase IIb/III, dose-ranging study conducted in Japan, in which patients on previously stable csDMARDs were randomized to receive upadacitinib 7.5, 15 or 30 mg once daily or matching placebo for a 12-week double-blind period. The primary endpoint was a 20% improvement in ACR criteria (ACR20) response at week 12 using non-responder imputation. Key secondary endpoints included ACR50, ACR70 and 28-joint DAS with CRP (DAS28-CRP) remission and low disease activity. Adverse events were also assessed.

Results: Of 197 patients treated, 187 completed the double-blind period. At week 12, more patients receiving upadacitinib 7.5, 15 or 30 mg vs placebo met the ACR20 response (75.5%, 83.7%, 80.0% vs 42.9%; P < 0.001), with significant differences observed as early as week 1. Stringent responses, including ACR50, ACR70 and DAS28-CRP <2.6, were achieved by significantly higher proportions of patients on upadacitinib than placebo and by numerically higher proportions on upadacitinib 15 or 30 mg vs upadacitinib 7.5 mg. Adverse events and infections (serious infections, opportunistic infections and herpes zoster) were more common with upadacitinib vs placebo and numerically highest with upadacitinib 30 mg. There were no venous thromboembolic events reported.

Conclusion: Efficacy of upadacitinib was demonstrated in this population of Japanese patients with RA and an inadequate response to csDMARDs. Safety and tolerability were consistent with other upadacitinib RA studies. The 15 mg dose of upadacitinib showed the most favourable benefit-risk profile.

Trial registration: ClinicalTrials.gov, https://ichgcp.net/clinical-trials-registry/NCT02720523.

Keywords: Janus kinase inhibitor; Japanese; efficacy; rheumatoid arthritis; safety; upadacitinib.

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig . 1
Fig. 1
Patient disposition
Fig . 2
Fig. 2
ACR20, ACR50 and ACR70 responses at week 12 (NRI) **P < 0.01, ***P < .001 vs PBO. NRI: non-responder imputation; PBO: placebo; UPA: upadacitinib.
Fig . 3
Fig. 3
Achievement of LDA and remission states at week 12 (NRI) *P < 0.05, **P < 0.01, ***P < .001 vs PBO. NRI: non-responder imputation; PBO: placebo; UPA: upadacitinib.
Fig . 4
Fig. 4
Change from baseline in patient-reported outcomes at week 12 HAQ-DI results are based on multiple imputation, other endpoints were based on MMRM analysis. *P < 0.05, **P < 0.01, ***P < 0.001 vs PBO. PBO: placebo; UPA: upadacitinib.

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Source: PubMed

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