Effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis based on large randomised trials: a systematic review and network meta-analysis.

Abstract

OBJECTIVE To quantify the effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis through a systematic review and Bayesian random-effects network meta-analysis. DESIGN We searched CENTRAL and regulatory agency websites (inception-2023) for large, English-language, randomised controlled trials (RCTs) (≥100 patients/group) examining any intra-articular intervention. PRIMARY OUTCOME pain intensity. SECONDARY OUTCOMES physical function and safety outcomes. Pain and function outcomes were analyzed at 2,6,12,24, and 52 weeks post-randomization, and presented as standardized mean differences (SMDs) (95% credible intervals, 95%CrI). The prespecified minimal clinically important between-group difference (MID) was -0.37 SMD. Safety outcomes were presented as odds ratios (OR) (95%CrI). FINDINGS Among 57 RCTs (22,795 participants) examining 18 intra-articular interventions, usual care or placebo, treatment effects were larger in high-risk-of-bias trials (n=35) than low/unclear-risk-of-bias trials (n=22). In the main analysis (excluding high-risk-of-bias trials), triamcinolone had the highest probabilities of reaching the MID at weeks 2-6 (75.3% and 90%, respectively) with corresponding SMDs of -0.48 (95%CrI,-0.85 to -0.10) and -0.53 (95%CrI,-0.79 to -0.27) compared to placebo. Tr14/Ze14 homeopathic product showed therapeutic potential at week 6 compared to placebo (SMD:-0.42, 95%CrI,-0.71 to -0.11, 63.5% probability of reaching the MID). Hyaluronic acid had higher risk of dropouts due to adverse events (OR:2.01, 95%CrI,1.08 to 3.77) and serious adverse events (OR:1.86, 95%CrI,1.16 to 3.03) than placebo. CONCLUSION Triamcinolone had the highest probabilities to have a treatment effect beyond the MID at weeks 2-6. Large RCTs with lower risk of bias do not support the notion that 16 other intra-articular interventions assessed improve pain or function beyond placebo effects in knee or hip OA. Lack of evidence of long-term effectiveness underscores the need for further research beyond 24-52 weeks.