title: Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To determine the rate of infection and all-cause mortality across tofacitinib phase II, phase III, and long-term extension (LTE) studies in patients with moderately to severely active rheumatoid arthritis (RA).
  
  
  METHODS
  Pooled data from studies of tofacitinib in patients with RA were analyzed. In these studies, tofacitinib was administered as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs. The cutoff date for inclusion of data was April 19, 2012.
  
  
  RESULTS
  Across phase II, phase III, and LTE studies, 4,789 patients received tofacitinib (8,460 patient-years of exposure). The overall rate of serious infection was 3.09 events per 100 patient-years (95% confidence interval [95% CI] 2.73-3.49), and rates were stable over time. A Cox proportional hazards model showed that age, corticosteroid dose, diabetes, and tofacitinib dose were independently linked to the risk of serious infection. Lymphocyte counts of <0.5 × 10(3) /mm(3) were rare but were associated with an increased risk of treated and/or serious infection. Overall, all-cause mortality rates were 0.30 events per 100 patient-years (95% CI 0.20-0.44).
  
  
  CONCLUSIONS
  The overall risk of infection (including serious infection) and mortality rates in RA patients treated with tofacitinib appear to be similar to those observed in RA patients treated with biologic agents. The rates of serious infection were stable over time.
authors.affiliation: Metroplex Clinical Research Center, Dallas, Texas.
authors.forename: Stanley
authors.initials: S
authors.lastname: Cohen
authors.forename: Sebastião C
authors.initials: SC
authors.lastname: Radominski
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gomez-Reino
authors.forename: Lisy
authors.initials: L
authors.lastname: Wang
authors.forename: Sriram
authors.initials: S
authors.lastname: Krishnaswami
authors.forename: Susan P
authors.initials: SP
authors.lastname: Wood
authors.forename: Koshika
authors.initials: K
authors.lastname: Soma
authors.forename: Chudi I
authors.initials: CI
authors.lastname: Nduaka
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kwok
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
authors.forename: Birgitta
authors.initials: B
authors.lastname: Benda
authors.forename: Richard
authors.initials: R
authors.lastname: Riese
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007239:Infections / Q000453:epidemiology* / Q000276:immunology / Q000401:mortality*; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D015995:Prevalence; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D008727:Methotrexate