TY - JOUR
T1 - Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to methotrexate
T2 - Results of a phase III randomised, double-blind, placebo-controlled trial (RAJ4) in Japan
AU - Takeuchi, Tsutomu
AU - Tanaka, Yoshiya
AU - Tanaka, Sakae
AU - Kawakami, Atsushi
AU - Iwasaki, Manabu
AU - Katayama, Kou
AU - Rokuda, Mitsuhiro
AU - Izutsu, Hiroyuki
AU - Ushijima, Satoshi
AU - Kaneko, Yuichiro
AU - Shiomi, Teruaki
AU - Yamada, Emi
AU - Van Der Heijde, Désirée
N1 - Funding Information:
1Keio University school of Medicine, Tokyo, Japan 2University of Occupational and environmental Health Japan, Kitakyushu, Japan 3The University of Tokyo, Tokyo, Japan 4nagasaki University Graduate school of Biomedical sciences, nagasaki, Japan 5Yokohama City University, Yokohama, Japan 6Katayama Orthopedic Rheumatology Clinic, asahikawa, Japan 7astellas Pharma inc, Tokyo, Japan 8leiden University Medical Center, leiden, The netherlands Acknowledgements The authors thank the patients who were involved in this study, as well as the investigators and the study team. a list of study centres is provided in the online supplementary information. The study was sponsored by astellas Pharma, inc. Writing and editorial support were provided by Derek Ho, PhD, and Rhian Harper Owen, PhD, for Cello Health Medergy, and were funded by astellas Pharma, inc.
Publisher Copyright:
© © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - DAS28
KW - disease activity
KW - methotrexate
KW - rheumatoid arthritis
KW - treatment
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U2 - 10.1136/annrheumdis-2019-215164
DO - 10.1136/annrheumdis-2019-215164
M3 - Article
C2 - 31350269
AN - SCOPUS:85070074782
SN - 0003-4967
VL - 78
SP - 1305
EP - 1319
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 10
ER -
