title: Heterogeneity in Comparisons of Discontinuation of Tumor Necrosis Factor Antagonists in Rheumatoid Arthritis - A Meta-Analysis.
abstract: OBJECTIVE
  We did a systematic review of studies comparing discontinuation of tumor necrosis factor alpha (TNF) antagonists in rheumatoid arthritis (RA) patients, pooled hazard ratios and assessed clinical and methodological heterogeneity.
  
  
  METHODS
  We searched MEDLINE and EMBASE until June 2015 for pairwise hazard ratios for discontinuing infliximab, etanercept, and adalimumab from cohorts of RA patients. Hazard ratios were pooled using inverse variance weighting and random effects estimates of the combined hazard ratio were obtained. Clinical and methodological heterogeneity was assessed using the between-subgroup I-square statistics and meta-regression.
  
  
  RESULTS
  Twenty-four unique studies were eligible and large heterogeneity (I-square statistics > 50%) was observed in all comparisons. Type of data, location, and order of treatment (first or second line) modified the magnitude and direction of discontinuation comparing infliximab with either adalimumab or etanercept; however, some heterogeneity remained. No effect modifier was identified when adalimumab and etanercept were compared.
  
  
  CONCLUSIONS
  Heterogeneity in studies comparing discontinuation of TNF antagonists in RA is partially explained by type of data, location, and order of treatment. Pooling hazard ratios for discontinuing TNF antagonists is inappropriate because largely unexplained heterogeneity was demonstrated when random effect estimates were calculated.
authors.affiliation: Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Anat
authors.initials: A
authors.lastname: Fisher
authors.affiliation: Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Family Practice, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ken
authors.initials: K
authors.lastname: Bassett
authors.affiliation: Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gautam
authors.initials: G
authors.lastname: Goel
authors.affiliation: Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Dana
authors.initials: D
authors.lastname: Stanely
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: M Alan
authors.initials: MA
authors.lastname: Brookhart
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Hugh R
authors.initials: HR
authors.lastname: Freeman
authors.affiliation: Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: James M
authors.initials: JM
authors.lastname: Wright
authors.affiliation: Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dormuth
mesh_terms: D000068879:Adalimumab / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068800:Etanercept / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept