Background/Purpose: Previously, several studies have meta-analyzed clinical, functional or structural efficacy of biologics in treating rheumatoid arthritis (RA) patients. However, the comparative efficacy of biologics in inhibiting radiographic progression from a long-term perspective is still not fully understood. We compared 1-year radiographic efficacy of biologics using a Bayesian network meta-analysis (NMA), and reviewed radiographic data for up to 10 years follow-up.

Methods: A systematic literature search of published peer-reviewed articles and scientific meeting abstracts identified randomized controlled trials investigating approved biologic therapies in combination with methotrexate (MTX) or tocilizumab alone in predominantly biologic-na•ve (< 20% biologic experienced) RA patients. Structural damage was analyzed as change from baseline using the modified van der Heijde Total Sharp Score (vdHS). One-year data were included in the NMA. Model parameters were estimated in a Bayesian framework using noninformative prior distributions. Longer term data (>1 year) was reviewed qualitatively in absence of sufficient data points for analysis. To assess the effect of biologic therapies in specific subpopulations, subgroup analyses were performed on: DMARD na•ve, DMARD inadequate responders, early RA, and established RA.

Results: Eleven clinical trials were identified and included in the NMA model. All biologics in combination with MTX showed decreased radiographic progression at 1 year compared to MTX alone, as defined by negative mean difference in vdHS change (Figure). Most interventions showed statistically significant effect, except for golimumab 50 mg every 4 weeks and tocilizumab 8mg/kg every 4 weeks.The largest statistically significant mean difference at 1 year was in adalimumab, where the increase in vdHS was 3.8 fewer units in patients administered adalimumab 40 mg every 2 weeks + MTX compared with those receiving MTX alone. Patients treated with infliximab 3 mg/kg every 8 weeks had the next highest relative effect at -3.7 versus MTX alone. Longer term radiographic data were found in 8 unique trials spanning 2 to 10 years of follow-up that demonstrate sustained slowing of radiographic progression for the following biologics (abatacept, certolizumab, etanercept, golimumab, infliximab and tocilizumab) in combination with MTX and adalimumab (+/-MTX). While the long term data did not contradict the efficacy of the 1-year outcomes, only 3 biologics (adalimumab,  golimumab, tocilizumab) had 5 years of follow-up and only adalimumab had 10 years of follow-up. Subgroup results yielded consistent findings.

Conclusion: Biologics generally inhibit the progression of structural damage from a long-term perspective. Although some biologics like adalimumab have demonstrated radiographic benefits for up to 10 years, more research is needed to replicate this finding.