Efficacy of Intra-articular Botulinum Toxin in Osteo-articular Joint Pain: A Meta-analysis of Randomized Controlled Trials

OBJECTIVE: This study was conducted with the aim of evaluating the efficacy of intra-articular injections of botulinum toxin type A (BT-A) into the painful joint diseases through a systematic review of the literature and a meta-analysis of controlled randomized trials. Intra-articular therapies (corticosteroids, hyaluronic acid) have limited efficacy and run a risk of toxicity in patients with joint pain. New therapeutic options are needed to treat painful osteoarticular disease. METHODS: We searched via Pubmed, American College of Rheumatology, and European League Against Rheumatism congresses, and gray literature for the studies reported until June 2016 and addressing the issue of BT intra-articular injections in patients with refractory joint pain. Randomized trials were included. For the meta-analysis, we compared a numeric rating scale (NRS) from 0 to 10 before treatment and at 1 or 2 months and 6 months after in the BT-A and the control groups for each study. We also compared separately low dose and high dose of BT at 1 or 2 months' evaluation. RESULTS: In a total of 269 selected articles, 8 were analyzed and 6 studies were included in the meta-analysis involving a total of 382 patients. On comparing the NRS rating for 5 trials, at 1 or 2 months irrespective of the dose of BT, 4 trials showed a positive effect of BT compared with the control on the NRS and 1 found no effect; the overall weighted mean difference [95% confidence interval (CI)] was -1.10 (-1.62, -0.58) (P<0.0001, I=63%). Among the 4 trials with a low dose of BT (100 U), comparing NRS at 1 or 2 months, 3 trials showed significant results with a positive effect of BT-A injection compared with the control on the NRS; the fourth study failed to find any effect. The overall weighted mean difference (95% CI) was -0.95 (-0.02, -1.88) (P=0.05, I=67%). In the 2 trials using a high dose of BT (200 U) comparing NRS at 1 or 2 months, there was an almost zero effect of BT, with an overall weighted mean difference (95% CI) of 0.13 (-0.55, 0.81) (P=0.71, I=0%). In the 3 trials comparing NRS at 6 months there was an overall weighted mean difference (95% CI) of -0.57 (-1.98, 0.83) (P=0.42, I=73%). CONCLUSIONS: BT-A intra-articular injections have short-term benefits with a statistically significant decrease in the NRS pain score of around 1 point in patients with refractory joint pain. A decrease in the pain score was also observed at 6 months but with a nonsignificant result.