title: Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis.
abstract: BACKGROUND
  Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis.
  
  
  METHODS
  In this phase 3, double-blind, placebo-controlled, parallel-group, 6-month study, 611 patients were randomly assigned, in a 4:4:1:1 ratio, to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, placebo for 3 months followed by 5 mg of tofacitinib twice daily, or placebo for 3 months followed by 10 mg of tofacitinib twice daily. The primary end points, assessed at month 3, were the percentage of patients with at least a 20% improvement in the American College of Rheumatology scale (ACR 20), the change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores (which range from 0 to 3, with higher scores indicating greater disability), and the percentage of patients with a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating more disease activity).
  
  
  RESULTS
  At month 3, a higher percentage of patients in the tofacitinib groups than in the placebo groups met the criteria for an ACR 20 response (59.8% in the 5-mg tofacitinib group and 65.7% in the 10-mg tofacitinib group vs. 26.7% in the combined placebo groups, P<0.001 for both comparisons). The reductions from baseline in HAQ-DI scores were greater in the 5-mg and 10-mg tofacitinib groups than in the placebo groups (-0.50 and -0.57 points, respectively, vs. -0.19 points; P<0.001). The percentage of patients with a DAS28-4(ESR) of less than 2.6 was not significantly higher with tofacitinib than with placebo (5.6% and 8.7% in the 5-mg and 10-mg tofacitinib groups, respectively, and 4.4% with placebo; P=0.62 and P=0.10 for the two comparisons). Serious infections developed in six patients who were receiving tofacitinib. Common adverse events were headache and upper respiratory tract infection. Tofacitinib treatment was associated with elevations in low-density lipoprotein cholesterol levels and reductions in neutrophil counts.
  
  
  CONCLUSIONS
  In patients with active rheumatoid arthritis, tofacitinib monotherapy was associated with reductions in signs and symptoms of rheumatoid arthritis and improvement in physical function. (Funded by Pfizer; ORAL Solo ClinicalTrials.gov number, NCT00814307.).
authors.affiliation: Metroplex Clinical Research Center, Dallas, TX 75231, USA. rfleischmann@arthdocs.com
authors.forename: Roy
authors.initials: R
authors.lastname: Fleischmann
authors.forename: Joel
authors.initials: J
authors.lastname: Kremer
authors.forename: John
authors.initials: J
authors.lastname: Cush
authors.forename: Hendrik
authors.initials: H
authors.lastname: Schulze-Koops
authors.forename: Carol A
authors.initials: CA
authors.lastname: Connell
authors.forename: John D
authors.initials: JD
authors.lastname: Bradley
authors.forename: David
authors.initials: D
authors.lastname: Gruben
authors.forename: Gene V
authors.initials: GV
authors.lastname: Wallenstein
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Zwillich
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kanik
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D004185:Disability Evaluation; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors*; D016018:Least-Squares Analysis; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D010880:Piperidines; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D004791:Enzyme Inhibitors; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053616:Janus Kinase 3