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.

Figure 1.. Patient disposition. AEs were categorized according to whether they were considered related to study drug or not. AE adverse event, BID twice daily.

Figure 2.. Response rates for patients receiving tofacitinib monotherapy or placebo over time. (a) ACR20 response (± SE), FAS, LOCF. (b) DAS28-4(ESR) < 2.6 (remission), 2.6–3.2 (LDA), > 3.2–< 5.1 (MDA), and ≥ 5.1 (HDA), FAS, no imputation. (c) DAS28-4(ESR) < 2.6 (remission) (± SE), FAS, no imputation. (d) Mean HAQ-DI (± SE) change from baseline, FAS. *p < 0.05 versus placebo. ACR20 American College of Rheumatology 20% improvement criteria, BID twice daily, DAS28-4(ESR) 28-joint disease activity score using erythrocyte sedimentation rate, FAS full analysis set, HAQ-DI Health Assessment Questionnaire-Disability Index, HDA high disease activity, LDA low disease activity, LOCF last observation carried forward, MDA medium disease activity, SE standard error.