Phase 3 Trial Supports Subcutaneous Anifrolumab in Systemic Lupus Erythematosus

A phase 3 trial showed that subcutaneous anifrolumab (Saphnelo) demonstrated significant, clinically meaningful treatment benefits for systemic lupus erythematosus (SLE) when added to standard therapy.1

“These meaningful results from the TULIP-SC trial provide confidence that the efficacy and DORIS-defined remission rates that we’ve seen with anifrolumab can be achieved in a new subcutaneous administration, allowing even more patients to benefit from this effective treatment,” said lead investigator Susan Manzi, MD, MPH, chair of the Allegheny Health Network (AHN) Medicine Institute and director of the Lupus Center of Excellence at the AHN Autoimmunity Institute, in a statement.2 “The results align with important changes in global lupus treatment recommendations, which now emphasize earlier intervention with biologics, driving remission and reduced use of oral corticosteroids as key treatment goals.”

Patients with SLE face an increased risk of early mortality, and approximately 50% develop irreversible organ damage within 5 years of diagnosis, largely driven by ongoing disease activity and chronic corticosteroid exposure. Reducing both disease activity and corticosteroid use lowers the risk of organ damage and other debilitating outcomes.1 The revised 2025 SLE recommendations identify achievement of DORIS remission as the primary treatment goal and strongly encourage corticosteroid discontinuation.3

Anifrolumab, a first-in-class, fully human monoclonal antibody that binds to subunit 1 of the type 1 interferon receptor and blocks the activity of type I IFN, is available in the US as an IV infusion administered by healthcare professionals.1 Subcutaneous anifrolumab allows patients to self-administer the treatment outside of the clinic; this form was approved in the EU in December 2025.

In the multinational, phase 3, double-blind, placebo-controlled TULIP-SC trial, investigators assessed the efficacy and safety of subcutaneous anifrolumab in adults aged 18 – 70 years with moderate-to-severe SLE despite being on standard therapy, such as oral corticosteroids, antimalarial, or immunosuppressants. The primary endpoint, tested in the pre-planned interim analysis with 220 patients (109 on anifrolumab and 111 on placebo), was the treatment difference in the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at 52 weeks.1

Participants were randomized 1:1 to receive 120 mg subcutaneous anifrolumab or placebo administered via a pre-filled, single-use syringe. A pre-specified interim analysis was performed once the first 220 participants reached Week 52. The study also included a 52-week open-label extension for participants who completed the initial 52-week treatment period.

The primary endpoint was met, with a difference of 59.4% for anifrolumab vs 43.9% for placebo (BICLA response difference, 15.5%; 95% confidence interval [CI], 2.3 – 28.6; P =.0211).1

The full analysis assessed secondary endpoints across 367 patients, with 184 on anifrolumab and 183 on placebo. More patients treated with anifrolumab vs placebo obtained a BICLA response while maintaining low or reduced oral glucocorticoid doses (≤ 7.5 mg per day) through week 52 (56.2% vs 34.0%; difference, 22.3%; 95% CI, 12.3 – 32.2; P <.0001). Patients on anifrolumab also had a reduced time to first sustained BICLA response (hazard ratio [HR], 2.2; 95% CI, 1.5 – 3.2; P <.0001).1

At Week 52, remission by DORIS criteria and attainment of a Low Lupus Disease Activity State were both significantly greater with anifrolumab than with placebo, with treatment differences of 14.2% (95% CI, 5.6 – 22.8; P =.0012) and 14.1% (95% CI, 4.6 – 23.6; P =.0038), respectively. Among patients on anifrolumab, 29% achieved DORIS remission and 40.1% attained low-disease activity.1

The anifrolumab arm had a slightly greater frequency of serious adverse events than placebo (11.9% vs 10.4); safety findings were consistent with the known clinical profile of intravenous anifrolumab. Herpes zoster occurred in 3.8% on anifrolumab vs 1.1% on placebo.1

“These results reinforce Saphnelo’s unique approach of targeting the type 1 interferon receptor to reduce disease activity, with the added convenience of subcutaneous self-administration,” said Sharon Barrr, executive vice president at BioPharmaceuticals R&D, AstraZeneca, in a statement. “The TULIP-SC findings build on the compelling body of evidence for Saphnelo, which has helped patients achieve remission and significantly reduce reliance on oral corticosteroids – further reinforcing our ambition to transform lupus care.”

References

1. Manzi S, Bruce IN, Morand EF, et al. Efficacy and Safety of Subcutaneous Anifrolumab in Systemic Lupus Erythematosus: the Randomized, Phase 3, TULIP-SC Study. Arthritis Rheumatol. Published online December 29, 2025. doi:10.1002/art.70041

2. Saphnelo self-administration TULIP-SC trial demonstrates statistically significant and clinically meaningful reduction in systemic lupus erythematosus disease activity. AstraZeneca. Published on January 6, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/saphnelo-self-administration-tulip-sc-trial-demonstrates-statistically-significant-clinically-meaningful-reduction-sle-disease-activity.html. Accessed January 9, 2026/

3. Sammaritano LR, Askanase A, Bermas BL, et al. 2025 American College of Rheumatology (ACR) Guideline for the Treatment of Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). Published online November 3, 2025. doi:10.1002/acr.25690