Biologics or Tofacitinib for Rheumatoid Arthritis in Incomplete Responders to Methotrexate or Other Traditional Disease-Modifying Anti-Rheumatic Drugs: A Systematic Review and Network Meta-Analysis

Cochrane Database of Systematic Reviews 2016 Issue 5. Art. No.: CD012183 [DOI: 10.1002/14651858.CD012183].

Treatment options for RA patients who are MTX/DMARD incomplete responders (IR) include other DMARDs, biologics or tofacitinib (TOF). However, there is a lack of head-to-head studies to show any important differences between these options in terms of benefits and harms. This review provides an update of the 2009 Cochrane overview and network meta-analysis (NMA) of biologics for RA.1Nine biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, and tocilizumab) and TOF were assessed versus comparator (MTX/DMARD/placebo or combination). The review included randomized controlled trials (RCTs) from The Cochrane Central Register of Controlled Trials (CENTRAL) (via The Cochrane Library Issue 6, June 2015), MEDLINE (1946 to June 2015) and EMBASE (1947 to June 2015). A total of 79 RCTs with 32,874 participants provided usable data. Biologic + MTX/DMARD provided statistically significant and clinically meaningful improvements versus comparator in ACR50, improvement in function (HAQ) and proportion of patients achieving remission (DAS <1.6 or DAS28 <2.6). A statistically significant reduction in radiographic progression was also observed, although given the reduction was small the clinical relevance is unclear. There was high quality evidence that biologic + MTX/DMARD was associated with statistically borderline significant increased risk of SAEs versus comparator. Results were inconclusive for whether biologics + MTX/DMARDs are associated with an increased risk of cancer or withdrawals due to AEs. The review also provides comparisons between TOF and biologics/other options, although the authors do not draw conclusions on these. 1. Singh JA, et al. Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Cochrane Database of Systematic Reviews 2009, Issue 10. [DOI: 10.1002/14651858.CD007848].