Overall and specific treatment effects of pharmacological interventions for hand osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the overall treatment effect of pharmacological interventions for hand osteoarthritis (OA), examined in randomised controlled trials (RCTs). This includes both the specific treatment effect (reflecting intrinsic efficacy) and the contextual effect (arising from the therapeutic context) of the interventions. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science up to 7 April 2025. RCTs comparing pharmacological interventions addressed in the European Alliance of Associations for Rheumatology (EULAR) or American College of Rheumatology (ACR) guidelines with placebo were included. The primary outcome was pain, and secondary outcomes were function and stiffness. Each outcome was pooled using random-effects models. RESULTS: A total of 34 RCTs involving 3,763 participants were included and investigated 15 pharmacological interventions. Among the 15 pharmacological interventions evaluated, topical NSAIDs demonstrated the greatest overall treatment effects on pain (standardised response mean [SRM] = -1.69, 95% CI -2.56 to -0.82), function (SRM = -0.99, 95% CI -1.13 to -0.85), and stiffness (SRM = -1.43, 95% CI -2.50 to -0.35). However, topical NSAIDs were superior to placebo only for improving function. Approximately 70% of the overall treatment effect of topical NSAIDs was attributable to contextual effects. CONCLUSION: Topical NSAIDs showed relatively greater overall treatment effects among the included pharmacological interventions for pain relief, functional improvement and stiffness reduction in hand OA. The effects were mainly attributable to the contextual effect. However, in the absence of head-to-head evidence, these findings should be interpreted cautiously for clinical decision-making.