SC Anifrolumab and Other Advances in Lupus, with Susan Manzi, MD, MPH

Subcutaneous anifrolumab (Saphnelo; AstraZeneca) delivered clinically meaningful efficacy in systemic lupus erythematosus (SLE), demonstrating its potential as a flexible treatment option in the phase 3 TULIP-SC trial.¹

Anifrolumab is a first-in-class monoclonal antibody that inhibits type I interferon signaling, previously approved for treating moderate-to-severe SLE in its intravenous formulation in 2021.² The multinational, phase 3, double-blind, placebo-controlled TULIP-SC trial 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 trial met its primary endpoint, demonstrating a higher British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response rate at 52 weeks with anifrolumab compared with placebo (59.4% vs 43.9%), corresponding to a treatment difference of 15.5% (95% CI, 2.3–28.6; P = .0211).¹

Participants treated with anifrolumab also achieved higher rates of Definition of Remission in SLE (DORIS) criteria and Low Lupus Disease Activity State at week 52, 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. Overall, 29% of patients receiving anifrolumab reached DORIS remission, and 40.1% achieved low disease activity.¹ Safety outcomes were consistent with the established profile of intravenous anifrolumab.

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 learn more about next steps with anifrolumab and further research she would like to see done. She also shared her excitement for further advances coming down the pike in 2026.

“Patients would like to have some control, not just taking a medication, but also, what can they do to help prevent flares in their disease or improve their outcomes. And I think we're learning there's probably a lot they can do, whether it's dietary modifications, behavioral modifications, that can even impact how effective the agents are that we give them,” Manzi said.

Manzi’s reported disclosures include AstraZeneca, Cartesian, Exagen Diagnostics, GSK, Lily, Lupus Foundation of America, and UCB.

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#!