Subcutaneous Anifrolumab Improves Outcomes in Systemic Lupus Erythematosus: Phase 3 trial

SLE is an inflammatory disease that remains chronic, with unpredictable activity, high morbidity, and the necessity for continued glucocorticoid therapy, making the development of effective targeted therapies necessary to improve control and decrease glucocorticoid burden. TULIP-SC was a phase 3 randomized, double-blind, multinational, placebo-controlled trial.

Adults with moderate-to-severe active SLE, on standard therapies, were randomized 1:1 to receive anifrolumab, a concentration of 120 mg administered subcutaneously, or placebo one time each week for 52 weeks. The primary outcome was the difference in BICLA response at Week 52 between the treatment groups. The primary outcome was formally tested in the pre-planned interim analysis, whereas key secondary and other endpoints were tested in the full analysis population.

Key findings

• The initial analysis was performed on 220 patients, 109 of whom received anifrolumab, while 111 received a placebo. As of this interim analysis, the primary endpoint was achieved.

• The BICLA response rate at Week 52 was 59.4% in the anifrolumab group compared with 43.9% in the placebo group.

• It translated into 15.5% treatment difference in favor of anifrolumab with 95% CI of 2.3-28.6% (p = 0.0211).

• The total number of patients in the full-analysis population was 367, of whom 184 were administered anifrolumab, while 183 patients were administered a placebo.

• More patients in the anifrolumab group significantly achieved BICLA response with low or reduced oral glucocorticoids compared with placebo at Week 52 (56.2% vs 34.0%), with a treatment difference of 22.3% (95% CI, 12.3-32.2%) (p < 0.0001).

• The time to achieve the first sustained BICLA response was significantly shorter with anifrolumab, witha hazard ratio of 2.2 (95% CI, 1.5-3.2) (p < 0.0001).

• Other significant clinical outcomes also favored anifrolumab. At Week 52, the treatment differences for Disease Activity in SLE (DORIS) remission were 14.2% (95% CI, 5.6-22.8%; p = 0.0012) in favor of anifrolumab.

• The Low Lupus Disease Activity State was higher in the anifrolumab group with a treatment difference of 14.1% (95% CI, 4.6-23.6%; p = 0.0038).

• The safety profile of subcutaneous anifrolumab was consistent with the profile of intravenous anifrolumab.

• Serious adverse events occurred in 11.9% of the patient group treated with anifrolumab compared with 10.4% in the patient group treated with placebo.

• There was an incidence of herpes zoster infection in 3.8% of the patient group treated with anifrolumab.

Subcutaneously administered anifrolumab demonstrated significant and clinically meaningful reductions in disease activity, remission, and glucocorticoid taper in patients with moderate to severe SLE treated with conventional therapy compared with intravenously administered anifrolumab in the TULIP trials, with a favorable safety profile and a mechanism of action consistent with IV dosing, representing a viable and convenient treatment alternative for chronic SLE treatment.

Reference:

Manzi, S., Bruce, I. N., Morand, E. F., Furie, R., Tanaka, Y., Kalunian, K. C., Askanase, A., Puzio, P., Khan, E., Wissmar, J., Song, M., Lindholm, C., & Investigators, T. T.-S. (2025). Efficacy and safety of subcutaneous anifrolumab in systemic lupus erythematosus: The randomized, phase 3, TULIP-SC study. Arthritis & Rheumatology, art.70041. https://doi.org/10.1002/art.70041