Biologics for rheumatoid arthritis: an overview of Cochrane reviews.
BACKGROUND
The biologic disease-modifying anti-rheumatic drugs (DMARDs) are very effective in treating rheumatoid arthritis (RA), however there is a lack of head-to-head comparison studies.


OBJECTIVE
To compare the efficacy and safety of abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab in patients with RA.


METHODS
This 'Overview of Reviews' was done by including all Cochrane Reviews on Biologics for RA available in The Cochrane Library. We included only data on standard dosing regimens for these biologic DMARDs from placebo-controlled trials. The primary efficacy and safety outcomes were ACR50 and withdrawals due to adverse events. We calculated Risk Ratios (RR) for efficacy, Odds Ratio (OR) for safety and combined estimates of events across the placebo groups as the expected Control Event Rate (CER). Indirect comparisons of biologics were performed for efficacy and safety using a hierarchical linear mixed model incorporating the most important study-level characteristic (i.e. type of biologic) as a fixed factor and study as a random factor; reducing the between study heterogeneity by adjusting for the interaction between the proportion of patients responding on placebo and the duration of the trial.


RESULTS
From the six available Cochrane reviews, we obtained data from seven studies on abatacept, eight on adalimumab, five on anakinra, four on etanercept, four on infliximab, and three on rituximab.The indirect comparison estimates showed similar efficacy for the primary efficacy outcome for all biologics with three exceptions. Anakinra was less efficacious than etanercept with a ratio of RRs (95% CI; P value) of 0.44 (0.23 to 0.85; P = 0.014); anakinra was less efficacious than rituximab, 0.45 (0.22 to 0.90; P = 0.023); and likewise adalimumab was more efficacious than anakinra, 2.34 (1.32 to 4.13; P = 0.003).In terms of safety, adalimumab was more likely to lead to withdrawals compared to etanercept, with a ratio of ORs of 1.89 (1.18 to 3.04; P = 0.009); anakinra more likely than etanercept, 2.05 (1.27 to 3.29; P = 0.003); and likewise etanercept less likely than infliximab, 0.37 (0.19 to 0.70; P = 0.002).


CONCLUSIONS
Based upon indirect comparisons, anakinra seemed less efficacious than etanercept, adalimumab and rituximab and etanercept seemed to cause fewer withdrawals due to adverse events than adalimumab, anakinra and infliximab. Significant heterogeneity in characteristics of trial populations imply that these finding must be interpreted with caution. These findings can inform physicians and patients regarding their choice of biologic for treatment of RA.
Singh
Jasvinder A
JA
Medicine, Minneapolis VA Medical Center, 1 Veterans Drive, Rheumatology (111R), Minneapolis, MN, USA, 55417.
Christensen
Robin
R
Wells
George A
GA
Suarez-Almazor
Maria E
ME
Buchbinder
Rachelle
R
Lopez-Olivo
Maria Angeles
MA
Tanjong Ghogomu
Elizabeth
E
Tugwell
Peter
P
D000069594:Abatacept; D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000009:adverse effects / Q000627:therapeutic use*; D000068800:Etanercept; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D000069285:Infliximab; D053590:Interleukin 1 Receptor Antagonist Protein / Q000009:adverse effects / Q000627:therapeutic use; D010349:Patient Compliance; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012196:Review Literature as Topic; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D001688:Biological Products; D018796:Immunoconjugates; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D018124:Receptors, Tumor Necrosis Factor; D000069283:Rituximab; D000069594:Abatacept; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept