Subcutaneous Anifrolumab Expands Treatment Flexibility for SLE, With Susan Manzi, MD, MPH

Subcutaneous (SC) anifrolumab (Saphnelo; AstraZeneca) demonstrated significant, clinically meaningful treatment benefits for systemic lupus erythematosus (SLE) when added to standard therapy in the phase 3 TULIP-SC trial.¹

Anifrolumab is a first-in-class monoclonal antibody targeting the type I interferon receptor, which has reshaped expectations for disease activity reduction and remission in moderate-to-severe SLE since its 2021 approval.² The TULIP-SC trial is endeavoring to extend that progress by demonstrating that anifrolumab can deliver comparable clinical benefits in a subcutaneous formulation, offering patients and clinicians a potentially more flexible option for long-term disease management.

TULIP-SC met its primary end point of British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at 52 weeks, 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

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

RheumatologyLive spoke with study 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, to discuss the key clinical takeaways from TULIP-SC. She emphasized why the subcutaneous formulation matters in real-world practice.

“Having the ability to do [either monthly IV or weekly SC], because some people would rather forget about any kind of medication and just go once a month and have their IV. and then there are all those patients that would much prefer just the flexibility and freedom of being able to do self injections weekly. So now we have a choice, and it's it's great for physicians and also for our patients,” Manzi said.

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 (anifrolumab) approved in the US for moderate to severe systemic lupus erythematosus. News release. AstraZeneca. August 2, 2021. https://www.astrazeneca.com/media-centre/press-releases/2021/saphnelo-approved-in-the-us-for-sle.html#!