Safety of Low-Dose Tanezumab in the Treatment of Hip or Knee Osteoarthritis: A Systemic Review and Meta-analysis of Randomized Phase III Clinical Trials.

Objectives: To evaluate the safety of low-dose tanezumab in the treatment of knee or hip osteoarthritis (OA).

Methods: Databases were searched up to September 2019 for phase III randomized controlled trials (RCTs). Eleven phase III RCTs comprising 11,455 patients were eligible. The pooled estimates of safety outcomes were assessed and expressed using relative risks (RRs) and 95% confidence intervals with a random-effects model.

Results: Tanezumab significantly increased the incidence of rapidly progressive OA (RPOA; RR = 9.07, 95% CI = 1.21-67.90, P = 0.03) and abnormal peripheral sensation (APS; RR = 2.68, 95% CI = 1.64-4.37, P < 0.00001) compared with placebo. No significant difference was found in terms of incidence of total joint replacement (TJR; RR = 1.13, 95% CI = 0.76-1.68, P = 0.55) or withdrawal due to adverse effects (AEs; RR = 1.26, 95% CI = 0.79-2.00, P = 0.33). The tanezumab group showed a statistically higher incidence of RPOA (RR = 3.96, 95% CI = 2.23-7.04, P < 0.00001) and APS (RR = 1.2, 95% CI = 1.44-2.56, P < 0.00001) compared with the nonsteroidal anti-inflammatory drugs and opioids group. No significant difference was found in terms of TJR (RR = 1.51, 95% CI = 0.65-3.47, P = 0.33) and withdrawal (RR = 0.54, 95% CI = 0.20-1.40, P = 0.20). Subgroup analysis revealed that 2.5 mg of tanezumab did not show an advantage over 5 mg of tanezumab in reducing AEs.

Conclusions: These results demonstrate that RPOA and APS should be the most concerning AEs when using tanezumab in OA patients. Additional data are needed to define the optimal dose to minimize risk and to determine the optimal subjects to receive this treatment.