Efficacy and safety of belimumab and anifrolumab in systemic lupus erythematosus: A systematic review and network meta-analysis.

To compare the efficacy and safety of belimumab and anifrolumab in adult patients with SLE. We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in SLE. We included RCTs comparing belimumab or anifrolumab plus standard of care versus placebo plus standard of care. Outcomes included SRI-4, BICLA, selected BILAG organ-domain responses, and safety endpoints; belimumab BICLA data were derived from post hoc analyses. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. Risk of bias was assessed with RoB 2; certainty in network estimates was evaluated using the GRADE approach as applied in the CINeMA framework. Eleven trials (n = 8607) were included (4 anifrolumab; 7 belimumab, including 2 safety-only trials). Both biologics were associated with higher odds of achieving an SRI-4 response than placebo: anifrolumab OR 1.78 (95% CI 1.41-2.24); belimumab OR 1.62 (95% CI 1.38-1.90), with no significant difference between active treatments. For BICLA, anifrolumab was superior to belimumab (OR 1.56, 95% CI 1.10-2.21). Mucocutaneous and musculoskeletal responses favored both biologics versus placebo, whereas renal and cardiovascular/respiratory effects were not statistically significantly different. In safety analyses, SAEs and serious infections were similar between biologics, whereas herpes zoster was higher with anifrolumab versus belimumab (OR 4.74, 95% CI 2.00-11.21). In this NMA, anifrolumab and belimumab achieved similar SRI-4 responses. Anifrolumab showed a higher BICLA response than belimumab, but this finding should be interpreted cautiously given reliance on indirect evidence and moderate certainty. Clinically, these data support individualized biologic selection, weighing potential benefit on BICLA against the consistently higher herpes zoster risk with anifrolumab.