Meta-analysis of belimumab versus anifrolumab in systemic lupus erythematosus and lupus nephritis

OBJECTIVE: Belimumab and anifrolumab are two biologic therapies currently employed in the management of systemic lupus erythematosus (SLE). Belimumab is approved for both SLE and lupus nephritis (LN), whereas anifrolumab is not currently approved for LN and has only been evaluated for LN in one published phase II trial. Direct head-to-head comparative data are lacking. This meta-analysis aims to indirectly compare the efficacy and safety of belimumab and anifrolumab using evidence from randomized controlled trials (RCTs). METHODS: We performed a comprehensive search of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Indirect comparative analyses were conducted using odds ratios (ORs) and hazard ratios (HRs) derived from clinical trial data comparing both belimumab and anifrolumab with placebo for SLE and LN. Primary endpoints included SRI‑4 response, SELENA-SLEDAI ≥ 4 reduction, corticosteroid dose reduction, incidence of severe flares, normalization of anti-dsDNA, and normalization of C3/C4 in SLE as well as complete renal response (CRR), renal event-free survival, and immunologic biomarkers in LN. Safety was evaluated based on the incidence of herpes zoster, serious infections, and mortality. RESULTS: Seven RCTs comprising 4332 patients treated with either belimumab or anifrolumab for SLE or LN were included in this meta-analysis. For SLE, belimumab demonstrated superior SRI‑4 response rates (OR = 1.99, 95% CI: 1.25-3.16) relative to anifrolumab, whereas anifrolumab yielded greater benefit in steroid tapering (OR = 0.31, 95% CI: 0.19-0.51) and immunologic normalization (anti-dsDNA: OR = 0.69, 95% CI: 0.43-1.10; C3/C4: OR = 0.69, 95% CI: 0.42-1.13). In LN, both agents improved CRR rates compared to placebo; however, indirect comparisons between the two agents were not definitive due to wide confidence intervals (CRR: OR = 0.83, 95% CI: 0.22-3.10). Safety profiles were similar in terms of serious infections and mortality, although anifrolumab was linked to higher rates of herpes zoster (7.2% vs. 3.2-4.6% for belimumab). CONCLUSION: Belimumab confers greater benefit in terms of SRI‑4 response for SLE, while anifrolumab is more effective for corticosteroid tapering and immunologic parameter normalization. In LN, the comparative efficacy remains uncertain. Both agents exhibit similar safety profiles, but anifrolumab is associated with an increased risk of herpes zoster. Differences in study design, inclusion criteria, and assessment protocols among included trials may limit direct comparability.