Comparative efficacy and safety of intravenous or subcutaneous belimumab in combination with standard therapy in patients with active systemic lupus erythematosus: a Bayesian network meta-analysis of randomized controlled trials

Abstract

Objective In this study, we aimed to assess the relative efficacy and safety of intravenous (IV) or subcutaneous (SC) belimumab compared with those of placebo in patients with active systemic lupus erythematosus (SLE). Methods We performed a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of belimumab 1mg/kg and 10mg/kg IV administration, and belimumab 200mg SC injection, and placebo in patients with active SLE despite having received standard therapy. Results Five RCTs (3460 patients) met the inclusion criteria. The SLE Responder Index (SRI) response rate at week 52 was significantly higher in the belimumab 10mg/kg group than in the placebo group (OR 2.63, 95% CrI 2.14-3.23). Similarly, the SRI response rates were significantly higher in the belimumab 1mg/kg, and belimumab 200mg SC groups than in the placebo group (OR 2.42, 95% CrI 1.90-3.09; OR 1.71, 95% CrI 1.27-2.29). Ranking probability based on surface under the cumulative ranking curve (SUCRA) indicated that belimumab 10mg/kg had the highest probability of being the best treatment for achieving the SRI response (SUCRA=0.9174), followed by belimumab 1mg/kg (SUCRA=0.7338), belimumab 200mg SC (SUCRA=0.3487), and placebo (SUCRA=0.0000). However, a sensitivity test by omitting one outlier study showing low SRI response rate compared with the other three studies (11% vs. 33%, 40%, 48%) showed that belimumab 200mg SC and belimumab 10mg/kg had the highest probability of being the best treatment for achieving the SRI response (SUCRA=0.7903, SUCRA=0.7456), followed by belimumab 1mg/kg, and placebo. The number of serious adverse events (SAEs) did not differ significantly among the four treatment options. Conclusions Belimumab at 1 and 10mg/kg IV and belimumab 200mg SC in combination with standard therapy was an efficacious intervention for active SLE, and was not associated with a significant risk of SAEs.