title: Tofacitinib or adalimumab versus placebo in rheumatoid arthritis.
abstract: BACKGROUND
  Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated for the treatment of rheumatoid arthritis.
  
  
  METHODS
  In this 12-month, phase 3 trial, 717 patients who were receiving stable doses of methotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, 40 mg of adalimumab once every 2 weeks, or placebo. At month 3, patients in the placebo group who did not have a 20% reduction from baseline in the number of swollen and tender joints were switched in a blinded fashion to either 5 mg or 10 mg of tofacitinib twice daily; at month 6, all patients still receiving placebo were switched to tofacitinib in a blinded fashion. The three primary outcome measures were a 20% improvement at month 6 in the American College of Rheumatology scale (ACR 20); the change from baseline to month 3 in the score on the Health Assessment Questionnaire-Disability Index (HAQ-DI) (which ranges from 0 to 3, with higher scores indicating greater disability); and the percentage of patients at month 6 who had 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 greater disease activity).
  
  
  RESULTS
  At month 6, ACR 20 response rates were higher among patients receiving 5 mg or 10 mg of tofacitinib (51.5% and 52.6%, respectively) and among those receiving adalimumab (47.2%) than among those receiving placebo (28.3%) (P<0.001 for all comparisons). There were also greater reductions in the HAQ-DI score at month 3 and higher percentages of patients with a DAS28-4(ESR) below 2.6 at month 6 in the active-treatment groups than in the placebo group. Adverse events occurred more frequently with tofacitinib than with placebo, and pulmonary tuberculosis developed in two patients in the 10-mg tofacitinib group. Tofacitinib was associated with an increase in both low-density and high-density lipoprotein cholesterol levels and with reductions in neutrophil counts.
  
  
  CONCLUSIONS
  In patients with rheumatoid arthritis receiving background methotrexate, tofacitinib was significantly superior to placebo and was numerically similar to adalimumab in efficacy. (Funded by Pfizer; ORAL Standard ClinicalTrials.gov number, NCT00853385.).
authors.affiliation: Karolinska Institute, Stockholm.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.forename: Roy
authors.initials: R
authors.lastname: Fleischmann
authors.forename: Stanley
authors.initials: S
authors.lastname: Cohen
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
authors.forename: Juan A
authors.initials: JA
authors.lastname: García Meijide
authors.forename: Sylke
authors.initials: S
authors.lastname: Wagner
authors.forename: Sarka
authors.initials: S
authors.lastname: Forejtova
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Zwillich
authors.forename: David
authors.initials: D
authors.lastname: Gruben
authors.forename: Tamas
authors.initials: T
authors.lastname: Koncz
authors.forename: Gene V
authors.initials: GV
authors.lastname: Wallenstein
authors.forename: Sriram
authors.initials: S
authors.lastname: Krishnaswami
authors.forename: John D
authors.initials: JD
authors.lastname: Bradley
authors.forename: Bethanie
authors.initials: B
authors.lastname: Wilkinson
mesh_terms: D000068879:Adalimumab; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; 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; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009504:Neutrophils; D010880:Piperidines; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D004791:Enzyme Inhibitors; D008074:Lipoproteins; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C030104:lipoprotein cholesterol; C479163:tofacitinib; D002784:Cholesterol; D053616:Janus Kinase 3; D000068879:Adalimumab; D008727:Methotrexate