Efficacy and Safety of Subcutaneous Anifrolumab in Systemic Lupus Erythematosus: A Randomized, Phase 3 Study

OBJECTIVE: The multinational, phase 3, double-blind, placebo-controlled TULIP-SC trial evaluated the efficacy and safety of subcutaneous anifrolumab in adults who have moderate to severe systemic lupus erythematosus (SLE) activity, despite receiving standard therapy. METHODS: Adults with SLE received subcutaneous anifrolumab 120 mg or placebo once weekly for 52 weeks (1:1 randomization). Only the primary endpoint (treatment difference in BILAG-based Composite Lupus Assessment [BICLA] response at 52 weeks) was formally tested in a preplanned interim analysis; key secondary and other endpoints were tested in the full analysis. RESULTS: At the interim analysis (220 patients, anifrolumab: n = 109; placebo: n = 111), the primary endpoint was met (anifrolumab vs placebo: 59.4% vs 43.9%; BICLA response difference 15.5%, 95% confidence interval [95% CI] 2.3-28.6; P = 0.0211). The full analysis included 367 patients (anifrolumab: n = 184; placebo: n = 183). Versus placebo, more patients treated with anifrolumab attained a BICLA response while maintaining low/reduced oral glucocorticoid doses through week 52 (56.2% vs 34.0%; difference 22.3%, 95% CI 12.3-32.2; P < 0.0001), and the time to first sustained BICLA response was reduced (hazard ratio 2.2, 95% CI 1.5-3.2; P < 0.0001). Treatment differences in week 52 DORIS remission and Low Lupus Disease Activity State attainment rates favored anifrolumab over placebo (14.2%, 95% CI 5.6-22.8; P = 0.0012, and 14.1%, 95% CI 4.6-23.6; P = 0.0038). The frequencies of serious adverse events were 11.9% with anifrolumab and 10.4% with placebo; the frequencies of herpes zoster were 3.8% and 1.1%, respectively. CONCLUSION: Consistent with the well-established profile of intravenous anifrolumab, subcutaneous anifrolumab demonstrated significant, clinically meaningful treatment benefits when added to standard therapy, and an acceptable safety profile in patients with moderate to severe SLE.