Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study

Abstract

Objectives. To evaluate oral tofacitinib versus placebo for treatment of active rheumatoid arthritis in Japanese patients with inadequate response to disease-modifying antirheumatic drugs.

Methods. In this double-blind, placebo-controlled, randomized, parallel-group, 12-week, phase 2 study (clinicaltrials.gov NCT00687193), 317 patients received tofacitinib: 1, 3, 5, 10, or 15 mg as monotherapy or placebo twice daily (BID). Primary endpoint: response rate by American College of Rheumatology (ACR) ≥ 20% improvement criteria (ACR20) at week 12.

Results. ACR20 response rates: 37.7% (20/53), 67.9% (36/53), 73.1% (38/52), 84.9% (45/53), and 90.7% (49/54) with tofacitinib: 1, 3, 5, 10, and 15 mg BID, respectively, versus 15.4% (8/52) with placebo (p < 0.01; all doses). Dose-dependent ACR20 responses with tofacitinib versus placebo occurred from week 2 onward (p < 0.05). Changes from baseline in 28-joint disease activity score using erythrocyte sedimentation rate improved with tofacitinib versus placebo from week 4 (p < 0.01; all doses). Six tofacitinib patients experienced treatment-related serious adverse events (AEs). Most common treatment-emergent AEs: nasopharyngitis (10% vs 12%) and hyperlipidemia (5% vs 0%). Serum creatinine, hemoglobin, and total-, low-, and high-density lipoprotein-cholesterol levels increased with tofacitinib.

Conclusions. Tofacitinib produced dose-dependent ACR20 responses and reduced disease activity. The safety profile was consistent with that reported from global monotherapy trials.

Keywords:

• Japan
• Monotherapy
• Randomized controlled trial
• Rheumatoid arthritis
• Tofacitinib

Acknowledgments

This study was sponsored by Pfizer Inc. The authors would like to thank the patients who were involved in this study, and the A3921040 investigators and study team. The authors would like to acknowledge Makoto Suzuki and Keiko Yazawa for their valuable contribution to the study, and So Miyoshi who supported design-operating characteristics work on this study. Medical writing support was provided by Jonny Miller and Kate Silverthorne at Complete Medical Communications and was funded by Pfizer Inc.

Conflict of interest

Y Tanaka has received consultancy fees, speaking fees, and honoraria from Abbvie, Chugai, Astellas, Takeda, Santen, MitsubishiTanabe, Pfizer, Janssen, Eisai, Daiichi-Sankyo, UCB Japan, GlaxoSmithKline, and Bristol-Myers-Squib.

T Takeuchi has received consultancy fees, speaking fees, and honoraria from Abbott Japan, AbbVie, Asahi Kasei Medical, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly Japan, Janssen Pharma, Mitsubishi Tanabe Pharma Corporation, Novartis, Pfizer, Symbio, Takeda, and UCB Japan.

H Yamanaka has received consultancy fees, speaking fees, and honoraria from AbbVie, AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Janssen Pharma, Mitsubishi Tanabe Pharma Corporation, Pfizer, and Takeda.

H Nakamura and S. Toyoizumi are employees of Pfizer Japan Inc, Tokyo, Japan.

S Zwillich is an employee of Pfizer Inc, Groton, USA.

Supplementary material available online

Supplementary Tables 1–2, Figures 1–3 and Supplementary Text.