Purpose: To methodologically review the published literature on rheumatoid arthritis multiple treatment comparison meta-analysis (MTCs). To identify methodological issues that can explain the substantial discrepancies in the findings of these MTCs.
Methods: We searched MEDLINE for rheumatoid arthritis multiple treatment comparisons. Following the PRISMA guidelines, we extracted a large set of methodological items from the identified reviews. These included, but were not limited to, inclusion/exclusion criteria, information sources (e.g., MEDLINE), choice of efficacy outcomes, approaches to dealing with differing response profiles to available treatments (e.g., DMARD-naïve vs DMARD inadequate response (IR)), approaches to monotherapies versus combination therapies, and approaches to dealing with potential covariate effect modifiers (i.e., sources of heterogeneity).
Results: We identified 13 published MTC, of which 9 were published since 2009. We identified major discrepancies in the estimated treatment effects across MTCs. For example, some treatments with almost identical effect estimates in one MTC could be significantly different in another. We identified major discrepancies in the inclusion of trials, despite highly similar eligibility criteria and literature searches. The number of included trials was typically much smaller than number of eligible trials at the time of publication. Six MTCs included patients of differing response profiled, and 3 of these inappropriately lumped DMARD-naïve and DMARD-IR patients in the analyses. Eight MTCs included considered both patients mono-therapy and combination therapy (ie, concomitant DMARD), but only 4 adjusted for the potential effect modification of giving concomitant DMARD Approximately half of the identified MTCs did not explore potential sources of heterogeneity. Among those that did, the explored sources were inconsistent. Lastly, most MTC only included one or two efficacy outcomes (e.g., ACR50) and only two considered health related quality of life outcomes (e.g., HAQ and DAS)
Conclusions: Major inconsistencies exist in the findings of published rheumatoid arthritis MTCs. The identified methodological shortcomings and inconsistencies may explain these inconsistencies. Further, there are many lessons to be learned from the identified shortcomings and the previous publications which can potentially strengthen the evidence base on comparative effectiveness between biologics for the treatment of rheumatoid arthritis.