Efficacy and safety of tofacitinib in Japanese patients with rheumatoid arthritis by background methotrexate dose: A post hoc analysis of clinical trial data

Abstract

Objectives: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We investigated concomitant methotrexate (MTX) dose on tofacitinib efficacy/safety in Japanese RA patients.

Methods: This post hoc analysis pooled data from a 3-month phase 2 study (NCT00603512) and a 24-month phase 3 study (NCT00847613). Patients (N= 254) received tofacitinib (low-dose (1 or 3 mg), 5 mg, 10 mg) twice daily (BID) or placebo, with low-dose (>0 to 8 mg/week) or high-dose (>8 mg/week) MTX. Efficacy (ACR20/50/70 and DAS28-4 (ESR)<2.6 response rates; changes from baseline (CFB) in DAS28-4 (ESR) and HAQ-DI) and safety (adverse events (AEs), discontinuations due to AEs, serious AEs, and deaths) were assessed through month 3.

Results: At month 3, ACR20/50/70 response rates, mean DAS28-4 (ESR) CFB and HAQ-DI CFB were similar across MTX doses and generally greater for all tofacitinib doses versus placebo. AE rates with low-dose/high-dose MTX were: placebo, 28.6%/52.9%; tofacitinib low-dose, 50.0%/66.7%; 5 mg BID, 56.5%/64.3%; 10 mg BID, 73.8%/67.7%.

Conclusion: Tofacitinib efficacy in Japanese RA patients may be unaffected by background MTX dose. AE rates with low-dose versus high-dose MTX were lower with placebo, tofacitinib low-dose or 5 mg BID, but not 10 mg BID, with no apparent differences across system organ class/laboratory parameters.

Keywords:

• Janus kinase
• Japan
• methotrexate
• rheumatoid arthritis
• tofacitinib

Conflict of interest

T. Takeuchi has received grants, consultancy fees, and/or speaking fees from AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, and Teijin. H. Yamanaka has received consultancy fees or speaking fees from AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Mitsubishi Tanabe, Pfizer, Takeda, and UCB. K. Yamaoka has received consultancy fees, speaking fees, and/or honoraria from Actelion, Astellas, Chugai, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer Inc, and Takeda. Y. Tanaka has received consultancy fees, speaking fees, and/or honoraria from AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Pfizer Inc, Sanofi, Takeda, Teijin, and YL Biologics, and has received research grants from AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, MSD, and Takeda. S. Toyoizumi and Y. Fukuma are employees of Pfizer Japan Inc. S. Arai, T. Hirose, and N. Sugiyama are employees and shareholders of Pfizer Japan Inc. R. DeMasi and S.H. Zwillich are employees and shareholders of Pfizer Inc.

Additional information

Funding

This study was funded by Pfizer Inc. Medical writing support, under the guidance of the authors, was provided by Stephanie Johnson, PhD, and Anthony G. McCluskey, PhD, at CMC Connect, a division of Complete Medical Communications Ltd, Glasgow, UK and was funded by Pfizer Inc, New York, NY, USA in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015; 163: 461–464).