Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III randomised, double-blind, placebo-controlled trial (RAJ4) in Japan.

Objective: To evaluate the efficacy and safety of the oral Janus kinase (JAK) inhibitor peficitinib versus placebo in Japanese patients with rheumatoid arthritis (RA).
Methods: In this multicentre, double-blind, parallel-group, placebo-controlled phase III study, patients with RA and inadequate response to methotrexate (MTX) were randomised 1:1:1 to placebo, peficitinib 100 mg once daily or peficitinib 150 mg once daily with MTX for 52 weeks. Based on baseline randomisation, at week 12, non-responders receiving placebo were switched to peficitinib until the end of treatment; the remaining patients were switched to peficitinib at week 28. Primary efficacy variables were American College of Rheumatology (ACR)20 response rate at week 12/early termination (ET) and change from baseline in van der Heijde-modified total Sharp score (mTSS) at week 28/ET.
Results: 519 patients were randomised and treated. Significantly more (p<0.001) peficitinib (58.6%, 100 mg; 64.4%, 150 mg) than placebo (21.8%) recipients achieved ACR20 response at week 12/ET. Significantly lower (p<0.001) mean changes from baseline in mTSS at week 28/ET occurred in peficitinib (1.62, 100 mg; 1.03, 150 mg) than placebo (3.37) recipients. Peficitinib was associated with haematological and biochemical parameter changes, and increased incidence of serious infections and herpes zoster-related disease. One death from suicide occurred in a patient in the placebo group after switching to peficitinib 100 mg.
Conclusions: In Japanese patients with RA and inadequate response to MTX, peficitinib demonstrated significant superiority versus placebo in reducing RA symptoms and suppressing joint destruction. Peficitinib had an acceptable safety and tolerability profile, with no new safety signals compared with other JAK inhibitors.
Trial Registration Number: NCT02305849.
Competing Interests: Competing interests: 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 KK; speaking fees from AbbVie GK, Bristol-Myers KK, Chugai Pharmaceutical Co, Ltd, Mitsubishi Tanabe Pharma Co, Pfizer Japan, Inc, Astellas Pharma, Inc, Daiichi Sankyo Co, Ltd, Eisai Co, Ltd, Sanofi KK, Teijin Pharma Ltd, Takeda Pharmaceutical Co, Ltd, and Novartis Pharma KK; consultancy fees from AstraZeneca KK, Eli Lilly Japan KK, Novartis Pharma KK, Mitsubishi Tanabe Pharma Co, AbbVie GK, Nippon Kayaku Co, Ltd, Janssen Pharmaceutical KK, Astellas Pharma, Inc, Taiho Pharmaceutical Co, Ltd, Chugai Pharmaceutical Co, Ltd, Taisho Toyama Pharmaceutical Co, Ltd, GlaxoSmithKline KK, and UCB Japan Co, Ltd. YT reports speaking fees and/or honoraria from Daiichi Sankyo, Astellas, Eli Lilly, Chugai, Sanofi, AbbVie, Pfizer, YL Biologics, Bristol-Myers, GlaxoSmithKline, UCB, Mitsubishi-Tanabe, Novartis, Eisai, Takeda, Janssen and Asahi Kasei, and research grants from Mitsubishi-Tanabe, Bristol-Myers, Eisai, Chugai, Takeda, AbbVie, Astellas, Daiichi Sankyo, Ono, MSD and Taisho Toyama. ST reports personal fees from Amgen, Inc, Asahi Kasei Pharma Corporation, Amgen Astellas BioPharma KK, Ono Pharmaceutical Co, Ltd, KYOCERA Medical Corporation, Daiichi Sankyo Co, Ltd, Teijin Pharma Ltd, Eli Lilly Japan KK 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, Japan Society for the Promotion of Science (JSPS)/Grant-in-Aid for Scientific Research (A), and JSPS/Grant-in-Aid for Exploratory Research outside the submitted work. AK has received 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; participated in speaker’s bureaux for AbbVie, Eisai, Takeda Pharmaceutical, Ono Pharmaceutical, Astellas Pharma, Mitsubishi Tanabe, Pfizer Japan, Chugai Pharmaceutical, MSD, and Bristol-Myers KK; and received consultancy fees from Astellas Pharma and Janssen Pharmaceutical KK. KK reports consultancy fees from Eisai Co, Ltd, and Toyama Chemical Co, Ltd and speaker fees from Daiichi Sankyo Co, Ltd, Astellas Pharma, Eli Lilly, Chugai, AbbVie, Pfizer, Bristol-Myers Squibb, UCB, Mitsubishi Tanabe, Takeda, Janssen, Asahi Kasei and AYUMI Pharmaceutical Corporation. MR, HI, SU, YK, TS and EY are employees of Astellas Pharma, Inc. MI has nothing to declare. DvdH has received consultancy honoraria from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB, and is the owner of Imaging Rheumatology.
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