Effects of biologic disease-modifying anti-rheumatic drugs on the radiographic progression of rheumatoid arthritis: a systematic literature review

Objective. To evaluate the effect of biologic disease-modifying anti-rheumatic drugs (bDMARDs) on radiographic progression in patients with rheumatoid arthritis (RA). Methods. A systematic review of electronic databases and conference proceedings was conducted through January 2015, to identify randomised controlled trials (RCTs) and observational studies that assessed the impact of bDMARDs [+/- conventional synthetic DMARDs (csDMARDs), mainly methotrexate (MTX)], versus csDMARDs alone, on radiographic progression in patients with RA. Results. Following screening of >5000 records, 104 publications covering 63 studies were included. Of 34 RCTs in patients with early, active (n=13) or established RA (n=21) [abatacept (1, 2); adalimumab (4, 2); certolizumab pegol (1, 4); etanercept (3, 3); golimumab (1, 4); infliximab (1, 1); rituximab (1, 1); tocilizumab (1, 5)], combination therapy with a bDMARD and MTX had a significantly greater effect than placebo or MTX alone, in inhibiting radiographic progression. This included patients previously unresponsive, or who responded incompletely, to MTX treatment alone, and was supported by data from observational studies. Findings from a smaller subset of these and other RCTs supported superiority of combination therapy over bDMARD monotherapy, and bDMARD monotherapy over MTX, in slowing radiographic progression. Conclusion. There is evidence from RCTs with a range of bDMARDs that improvement in radiographic outcomes for patients with early or established RA, when used in combination with MTX and to a lesser extent as monotherapy, are significantly greater than MTX alone. There was no evidence of a difference between bDMARDs on inhibition of radiographic progression.