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.

• Authors: Yoshiya Tanaka, Tsutomu Takeuchi, Hisashi Yamanaka, Hiroyuki Nakamura, Shigeyuki Toyoizumi, Samuel Zwillich
• Journal: Modern rheumatology (Mod Rheumatol) Vol. 25 Issue 4 Pg. 514-21 (Jul 2015) ISSN: 1439-7609 [Electronic] England
• PMID: 25496464 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antirheumatic Agents
• Piperidines
• Protein Kinase Inhibitors
• Pyrimidines
• Pyrroles
• tofacitinib
• Janus Kinase 3

Topics

• Adult
• Aged
• Antirheumatic Agents (administration & dosage)
• Arthritis, Rheumatoid (drug therapy)
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Janus Kinase 3 (antagonists & inhibitors)
• Japan
• Male
• Middle Aged
• Piperidines (administration & dosage)
• Protein Kinase Inhibitors (administration & dosage)
• Pyrimidines (administration & dosage)
• Pyrroles (administration & dosage)
• Time Factors
• Treatment Outcome