title: Indirect comparison of biological treatments in refractory rheumatoid arthritis.
abstract: OBJECTIVE
  A number of biological treatments are available for rheumatoid arthritis. They are effective some patients but their comparative efficacy is inadequately evaluated. Our aim was to compare the efficacy of adalimumab, etanercept, infliximab, abatacept, tocilizumab, golimumab and certolizumab pegol in rheumatoid arthritis, refractory to disease-modifying antirheumatic drugs (DMARDs), through a systematic review of published trials.
  
  
  METHODS
  As there were no direct comparisons, we searched for studies with similar characteristics to identify trials with results suitable for indirect comparison. Randomized, placebo-controlled pivotal clinical trials, with reported American College of Rheumatology ACR50 data at 24/30 weeks as efficacy endpoint, approved clinical doses and patients resistant to DMARDs who had not previously received other biological treatments were included. ACR50 was defined as the primary endpoint for the indirect comparison, with ACR20 and ACR70 as secondary endpoints. When two or more trials on one same drug were available, and a combined analysis was performed when appropriate. In the indirect comparison, the Bucher adjusted method was used with etanercept as reference drug. In the equivalence study, the equivalence window was a response efficacy difference of 15% between the alternatives.
  
  
  CONCLUSIONS
  Ten trials were found suitable for detailed analysis. In the clinical trials, all the biological drugs were seen to be more effective than placebo. Indirect comparison based on the ACR50 efficacy criterion all biological treatments showed similar results within the defined equivalence Δ value. The absolute efficacy difference (reduction of absolute risk, RAR) versus etanercept being 2·6% with adalimumab, 14% with infliximab, 11·6% with abatacept, 3% with tocilizumab, 12·4% with golimumab and 6·5% with certolizumab pegol.
  
  
  CONCLUSIONS
  The biological drugs used in rheumatoid arthritis are no different in efficacy. Their therapeutic positioning depends on their relative safety and convenience profiles.
authors.affiliation: Pharmacy Department, Hospital SAS La Línea and Hospital Punta Europa, Cádiz, Spain. myriam@asisur.com
authors.forename: M
authors.initials: M
authors.lastname: Gallego-Galisteo
authors.forename: A
authors.initials: A
authors.lastname: Villa-Rubio
authors.forename: E
authors.initials: E
authors.lastname: Alegre-del Rey
authors.forename: E
authors.initials: E
authors.lastname: Márquez-Fernández
authors.forename: J J
authors.initials: JJ
authors.lastname: Ramos-Báez
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000009:adverse effects / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D006801:Humans; D007136:Immunoglobulins / Q000009:adverse effects / Q000627:therapeutic use; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001688:Biological Products; D007136:Immunoglobulins; D011994:Recombinant Proteins; D008727:Methotrexate