Combined intra-articular injection of corticosteroid and hyaluronic acid reduces pain compared to hyaluronic acid alone in the treatment of knee osteoarthritis

Purpose: Intra-articular injections of corticosteroid (CS) and hyaluronic acid (HA) have individually demonstrated efficacy for knee osteoarthritis (OA); however, both treatments are limited by the trajectory of symptom relief. The combination of CS and HA in the management of knee OA may provide improved symptomatic relief for patients who are candidates for intra-articular therapies.

Methods: Electronic databases Medline, EMBASE and Cochrane Library were used to identify relevant publications. Randomized controlled trials (RCT) that evaluated intra-articular injections of combined CS and HA in comparison to HA alone were included. Outcomes eligible for meta-analysis were WOMAC pain, WOMAC total, OMERACT-OARSI responder rate, and treatment-related adverse events. Standardized mean differences (SMD) were calculated for continuous outcomes using an inverse variance method and a random-effects model. Odds ratios (OR) were calculated for dichotomous outcomes using the Mantel-Haenszel method and a random-effects model. Heterogeneity was assessed using the I² statistic.

Results: Eight trials (n = 751 patients) were included. Reduction in WOMAC pain scores at 2-4 weeks favoured the combined CS and HA group compared to HA alone [SMD 0.60, 95% CI (0.23, 0.97); p = 0.002, I² = 75%]. Longer term improvements at 24-26 and 52 weeks WOMAC pain scores also favoured the combined CS and HA group {[SMD 0.25, 95% CI (0.09, 0.41); p = 0.002, I² = 0%] and [SMD 0.39, 95% CI (0.01, 0.77); p = 0.05, I² = 0%]} compared to HA alone, respectively. There were no significant differences in WOMAC total scores, OMERACT-OARSI responder rate, or treatment-related adverse events.

Conclusion: Combined intra-articular injections of CS and HA led to reductions in pain at 2-4, 24-26 and 52 weeks compared to HA injections alone.

Level of evidence: Level II-meta-analysis.