title: Efficacy of initial methotrexate monotherapy versus combination therapy with a biological agent in early rheumatoid arthritis: a meta-analysis of clinical and radiographic remission.
abstract: OBJECTIVE
  The target outcome in early rheumatoid arthritis (ERA) is now remission. This meta-analysis compared the efficacy of initial methotrexate monotherapy versus combination therapy (methotrexate plus biological agent) for clinical remission and radiographic non-progression among ERA patients with minimal or no previous methotrexate exposure.
  
  
  METHODS
  A systematic search was performed for randomised controlled trials of ERA using predefined criteria. A random effects model was used to pool the risk ratio (RR) for clinical and radiographic remission at 52-56 weeks of follow-up.
  
  
  RESULTS
  Seven trials of combination therapy with infliximab, adalimumab, etanercept or abatacept were included. The majority of studies defined clinical remission as a 28-joint disease activity score (DAS28) of 2.6 or less. Radiographic non-progression was primarily defined as a modified total Sharp score change of less than 0.5 units. All trials demonstrated risk estimates in favour of combination therapy: the pooled RR for achieving clinical remission was 1.74 (95% CI 1.54 to 1.98) and for radiographic non-progression was 1.30 (95% CI 1.01 to 1.68). Significant heterogeneity among studies for the latter outcome was detected (p<0.001).
  
  
  CONCLUSIONS
  The efficacy of combination therapy with a biological agent is superior to methotrexate monotherapy for remission. Combination therapy has a greater initial effect on clinical remission than radiographic non-progression. Uniform definitions of remission are needed and the proportion of subjects who achieve the combined endpoint of clinical and radiographic remission should be considered as a meaningful outcome in future studies of ERA.
authors.affiliation: MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, Joseph and Wolf Lebovic Building, Toronto, Ontario M5T 3L9, Canada. bindee.kuriya@gmail.com
authors.forename: B
authors.initials: B
authors.lastname: Kuriya
authors.forename: E V
authors.initials: EV
authors.lastname: Arkema
authors.forename: V P
authors.initials: VP
authors.lastname: Bykerk
authors.forename: E C
authors.initials: EC
authors.lastname: Keystone
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018450:Disease Progression; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D008727:Methotrexate