Effi cacy and safety of tofacitinib as monotherapy in japanese patients with active rheumatoid arthritis

A 12-week, randomized, phase 2 study

Yoshiya Tanaka, Tsutomu Takeuchi, Hisashi Yamanaka, Hiroyuki Nakamura, Shigeyuki Toyoizumi, Samuel Zwillich

Research output: Contribution to journalArticle

56 Citations (Scopus)

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-choles-terol levels increased with tofacitinib. Conclusions. Tofacitinib produced dose-dependent ACR20 responses and reduced disease activity. The safety profi le was consistent with that reported from global monotherapy trials.

Original languageEnglish
Pages (from-to)514-521
Number of pages8
JournalModern Rheumatology
Volume25
Issue number4
DOIs
Publication statusPublished - 2015

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compound A 12
Rheumatoid Arthritis
Safety
Placebos
Nasopharyngitis
Antirheumatic Agents
tofacitinib
Joint Diseases
Blood Sedimentation
HDL Lipoproteins
Hyperlipidemias
LDL Lipoproteins
Creatinine
Hemoglobins
Therapeutics
Serum

Keywords

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

ASJC Scopus subject areas

  • Rheumatology

Cite this

Effi cacy and safety of tofacitinib as monotherapy in japanese patients with active rheumatoid arthritis : A 12-week, randomized, phase 2 study. / Tanaka, Yoshiya; Takeuchi, Tsutomu; Yamanaka, Hisashi; Nakamura, Hiroyuki; Toyoizumi, Shigeyuki; Zwillich, Samuel.

In: Modern Rheumatology, Vol. 25, No. 4, 2015, p. 514-521.

Research output: Contribution to journalArticle

Tanaka, Yoshiya ; Takeuchi, Tsutomu ; Yamanaka, Hisashi ; Nakamura, Hiroyuki ; Toyoizumi, Shigeyuki ; Zwillich, Samuel. / Effi cacy and safety of tofacitinib as monotherapy in japanese patients with active rheumatoid arthritis : A 12-week, randomized, phase 2 study. In: Modern Rheumatology. 2015 ; Vol. 25, No. 4. pp. 514-521.
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AU - Zwillich, Samuel

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AB - 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-choles-terol levels increased with tofacitinib. Conclusions. Tofacitinib produced dose-dependent ACR20 responses and reduced disease activity. The safety profi le was consistent with that reported from global monotherapy trials.

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