Cutaneous efficacy and glucocorticoid-sparing effects of anifrolumab in systemic lupus erythematosus: a systematic review and meta-analysis of randomized controlled trials.

Objective: To evaluate the cutaneous efficacy and glucocorticoid-sparing effects of anifrolumab in systemic lupus erythematosus (SLE) and to assess composite disease activity and flare-related and safety outcomes. Methods: PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched through 20 April 2026. Meta-analyses were restricted to randomized controlled trials comparing intravenous anifrolumab 300 mg every 4 weeks plus standard therapy with placebo plus standard therapy; TULIP-SC and overlapping reports were synthesized narratively. Risk ratios (RRs) or rate ratios with 95% confidence intervals (CIs) were pooled using random-effects models in the primary analyses, with fixed-effect models applied in sensitivity analyses. Modified Hartung-Knapp-Sidik-Jonkman (HKSJ) sensitivity analyses were performed for outcomes with substantial heterogeneity and a small number of contributing studies. Risk of bias and certainty of evidence were assessed using RoB 2 and GRADE, respectively. Results: In all, 12 reports from five independent trials were included; four intravenous trials contributed up to 1,203 participants. The Week 52 CLASI-A50 estimate was based on two trials (n = 165), not the full 1,203-participant IV evidence set. Random-effects pooling showed that anifrolumab improved Week 52 CLASI-A50 response based on two trials among patients with baseline CLASI-A ≥ 10 (RR 1.52, 95% CI 1.04 to 2.24), sustained oral glucocorticoid reduction in those receiving ≥ 10 mg/day at baseline (RR 1.56, 95% CI 1.30 to 1.87), and BICLA response (RR 1.66, 95% CI 1.41 to 1.94). SRI-4 (RR 1.39, 95% CI 1.04 to 1.87; I² = 80.8%), LLDAS attainment (RR 1.80, 95% CI 1.19 to 2.73; I² = 57.2%), and annualized flare rate (rate ratio 0.65, 95% CI 0.47 to 0.91; I² = 56.5%) favored anifrolumab but were affected by heterogeneity or limited trial numbers. The incidence of any adverse events was slightly higher (RR 1.09, 95% CI 1.03 to 1.16), whereas serious adverse events and discontinuations due to adverse events did not differ significantly. Supplementary analyses of selected adverse events of clinical interest suggested an increased risk of herpes zoster (RR 3.88, 95% CI 1.70 to 8.89), although event numbers were limited and these analyses were supplementary. Modified HKSJ sensitivity analyses yielded wider intervals crossing the null for SRI-4, LLDAS, annualized flare rate, serious adverse events, and adverse events leading to discontinuation. Conclusions: Intravenous anifrolumab improved Week 52 CLASI-A50 response in the two contributing trials of patients with baseline CLASI-A ≥ 10 and facilitated sustained glucocorticoid reduction in the prespecified glucocorticoid subgroup. DerSimonian-Laird point estimates for secondary efficacy outcomes generally favored anifrolumab, but the HKSJ sensitivity analyses for heterogeneous outcomes and the limited safety data warrant cautious interpretation. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261367219.