Subcutaneous Anifrolumab and Aiming for Remission in SLE, with Susan Manzi, MD, MPH

Subcutaneous anifrolumab (Saphnelo; AstraZeneca) significantly improved clinical outcomes in patients with systemic lupus erythematosus (SLE) when added to standard therapy, according to results from the phase 3 TULIP-SC trial.¹

Anifrolumab is a first-in-class monoclonal antibody that inhibits type I interferon signaling and has shifted treatment expectations for disease control and remission in moderate-to-severe SLE since its initial approval in 2021.² TULIP-SC was designed to determine whether these benefits could be replicated with a subcutaneous formulation, potentially expanding flexibility and convenience for long-term lupus management.

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

Patients receiving anifrolumab were also more likely to achieve a BICLA response while maintaining low or reduced oral glucocorticoid doses (≤7.5 mg/day) through week 52 than those receiving placebo (56.2% vs 34.0%; difference, 22.3%; 95% CI, 12.3–32.2; P < .0001). Time to first sustained BICLA response was shorter in the anifrolumab group (hazard ratio, 2.2; 95% CI, 1.5–3.2; P < .0001).¹

At week 52, rates of remission defined by the Definition of Remission in SLE (DORIS) criteria and achievement of a Low Lupus Disease Activity State were both significantly higher 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. 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. Serious adverse events occurred in 11.9% of patients in the anifrolumab group compared with 10.4% in the placebo group, and herpes zoster was reported in 3.8% and 1.1% of patients, respectively.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 data seen in TULIP-SC and how its measures align with the greater shift in the lupus field of aiming for remission instead of control.

“We're trying to not just give patient a medication and guess whether or not I think they're better… [Treating to target] gives these high bars that we set for ourselves to make sure we get there. And what I like about those metrics is they also require low to no steroid, so you're coupling really good response from the disease activity, but also on the background of little to no steroid. That's a game changer for us,” 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#!