Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to conventional DMARDs: a randomised, double-blind, placebo-controlled phase III trial (RAJ3).

Objectives: To investigate the efficacy and safety of peficitinib, an oral Janus kinase inhibitor, in patients with rheumatoid arthritis (RA).
Methods: In this double-blind phase III study, patients with RA and an inadequate response to prior disease-modifying anti-rheumatic drugs (DMARDs) were randomised to peficitinib 100 mg once daily, peficitinib 150 mg once daily, placebo or open-label etanercept for 52 weeks' treatment; placebo-treated patients were switched at week 12 to peficitinib 100 or 150 mg once daily. The primary endpoint was American College of Rheumatology (ACR)20 response at week 12/early termination (ET). Secondary endpoints (assessed throughout) included ACR20, ACR50 and ACR70 response, changes from baseline in disease activity scores (DAS)28 and ACR core parameters, adverse events (AEs) and changes in clinical or laboratory measurements.
Results: In total, 507 patients received treatment. ACR20 response rates at week 12/ET were significantly higher in the peficitinib 100 mg (57.7%) and 150 mg (74.5%) groups versus placebo (30.7%) (p<0.001). ACR50/70 response rates were also higher for both peficitinib doses versus placebo. Improvements in ACR response were maintained until week 52. Changes from baseline in DAS28-C-reactive protein/erythrocyte sedimentation rate and the ACR core set were significantly greater for both peficitinib doses versus placebo at week 12/ET (p<0.001). AE incidence was similar across treatment arms. Incidence of serious infection and herpes zoster-related disease was higher with peficitinib versus placebo, but with no clear dose-dependent increase.
Conclusions: In patients with RA and inadequate response to DMARDs, peficitinib 100 mg once daily or 150 mg once daily was efficacious in reducing RA symptoms and was well tolerated compared with placebo.
Trial Registration Number: NCT02308163.
Competing Interests: Competing interests: YT reports speaking fees and/or honoraria from Daiichi Sankyo, Astellas, Eli Lilly, Chugai, Sanofi, AbbVie, Pfizer, YL Biologics, Bristol-Myers Squibb, GlaxoSmithKline, UCB, Mitsubishi-Tanabe, Novartis, Eisai, Takeda, Janssen and Asahi Kasei, and research grants from Mitsubishi Tanabe, Bristol-Myers Squibb, Eisai, Chugai, Takeda, AbbVie, Astellas, Daiichi Sankyo, Ono, MSD and Taisho Toyama. TT has received grants from Astellas Pharma, Inc., Chugai Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd, Takeda Pharmaceutical Co. Ltd, AbbVie GK, Asahi Kasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan, Inc., Eisai Co. Ltd, AYUMI Pharmaceutical Corp., Nippon Kayaku Co. Ltd, and Novartis Pharma K.K.; speaking fees from AbbVie GK, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co. Ltd, Mitsubishi Tanabe Pharma Co., Pfizer Japan, Inc., Astellas Pharma, Inc., Daiichi Sankyo Co. Ltd, Eisai Co. Ltd, Sanofi K.K., Teijin Pharma Ltd, Takeda Pharmaceutical Co. Ltd, and Novartis Pharma K.K.; consultancy fees from Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., AbbVie GK, Nippon Kayaku Co. Ltd, Janssen Pharmaceutical K.K., Astellas Pharma, Inc., Taiho Pharmaceutical Co. Ltd, Chugai Pharmaceutical Co. Ltd, Taisho Toyama Pharmaceutical Co. Ltd, GlaxoSmithKline K.K., and UCB Japan Co. Ltd. ST reports personal fees from Amgen, Inc., Asahi Kasei Pharma Corporation, Amgen Astellas BioPharma K.K., Ono Pharmaceutical Co. Ltd, KYOCERA Medical Corporation, Daiichi Sankyo Co. Ltd, Teijin Pharma Ltd, Eli Lilly Japan K.K., and Pfizer Japan, Inc.; endowments from Astellas Pharma, Inc., AYUMI Pharmaceutical Corporation, Pfizer Japan, Inc., Bristol-Myers Squibb, Daiichi Sankyo Co. Ltd, and Chugai Pharmaceutical Co. Ltd; and grants from Japan Agency for Medical Research and Development (AMED), Japan Society for the Promotion of Science (JSPS)/Grant-in-Aid for Scientific Research (A), and Japan Society for the Promotion of Science (JSPS)/Grant-in-Aid for Exploratory Research outside the submitted work. AK reports grants from AbbVie, Eisai, Mitsubishi-Tanabe, Pfizer Japan, Takeda Pharmaceutical, Astellas Pharma, MSD, Ono Pharmaceutical, Teijin Pharma, Kyowa Hakko-Kirin, Sumitomo-Dainippon Pharma, Kissei Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Otsuka Pharmaceutical, Chugai Pharmaceutical, Santen Pharmaceutical and Daiichi Sankyo; participation in speakers’ bureaux for AbbVie, Eisai, Takeda Pharmaceutical, Ono Pharmaceutical, Astellas Pharma, Mitsubishi-Tanabe, Pfizer Japan, Chugai Pharmaceutical, MSD, and Bristol-Myers Squibb K.K.; and consultant fees from Astellas Pharma and Janssen Pharmaceutical K.K. YWS reports a grant from Astellas Pharma, Inc.YHC reports grants for research and clinical trials from Taiwan Ministry of Science and Technology, Taiwan Department of Health, Taichung Veterans General Hospital, National Yang-Ming University, GlaxoSmithKline, Pfizer, Bristol-Myers Squibb, Novartis, AbbVie, Johnson & Johnson, Roche, Sanofi, Chugai Pharma Taiwan Ltd, Boehringer Ingelheim, UCB, MSD, AstraZeneca and Astellas; and honoraria and consultant fees from Pfizer, Novartis, AbbVie, Johnson & Johnson, Bristol-Myers Squibb, Roche, Lilly, GlaxoSmithKline, AstraZeneca, Sanofi, MSD, Chugai Pharma Taiwan Ltd, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma and Thermo Fisher. MR, HI, SU, YK, RA, TS and EY are employees of Astellas Pharma, Inc.
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