Conventional and biologic disease-modifying anti-rheumatic drugs for osteoarthritis: a meta-analysis of randomized controlled trials

OBJECTIVES: The role of inflammation in OA is controversial and it is unclear whether suppressing inflammation with conventional or biologic DMARDs is effective. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to compare DMARDs with placebo in participants with symptomatic OA. METHODS: Databases (Medline, Embase, Allied and Complementary Medicine Database, Web of Science and Cochrane Library), conference abstracts and ClinicalTrials.gov were searched to end of November 2017 for placebo-controlled RCTs of DMARDs, including biologics, in symptomatic OA. Pain data at treatment peak time point were extracted and combined using a random-effects meta-analysis. Markers of inflammation and adverse events were extracted and reviewed. Risk of bias assessment was conducted using Cochrane’s tool. RESULTS: Eleven RCTs (1205 participants) were meta-analysed, including six for conventional DMARDs (757 participants) and five for biologics (448 participants). Overall, DMARDs were statistically superior to placebo [effect size (ES) = 0.18, 95% CI: 0.03, 0.34], although the difference was not clinically significant (0.5 ES threshold). Furthermore, no statistically significant differences were observed in sub-analysis of high-quality trials (ES = 0.11, 95% CI : −0.06, 0.28), biologics (ES = 0.16, 95% CI: −0.02, 0.34) or conventional DMARDs (ES = 0.24, 95% CI: −0.05, 0.54). No difference was found between erosive vs non-erosive hand OA, hand vs knee OA or anti-IL1 vs anti-TNF biologics. CONCLUSION: DMARDs did not offer clinically significant pain relief above placebo in OA. This poor efficacy indicates that inflammation may not be a prime driver for OA pain.