title: Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.affiliation: The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health , Kitakyushu, Fukuoka , Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Toyoizumi
authors.forename: Samuel
authors.initials: S
authors.lastname: Zwillich
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors; D007564:Japan; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053616:Janus Kinase 3
keywords: Japan; Monotherapy; Randomized controlled trial; Rheumatoid arthritis; Tofacitinib