A recent phase 3 trial has demonstrated that subcutaneous anifrolumab (Saphnelo) offers significant treatment benefits for patients with systemic lupus erythematosus (SLE) when combined with standard therapy. The findings from the TULIP-SC trial indicate that this new subcutaneous administration can lead to meaningful improvements in disease management for a wider range of patients.
Susan Manzi, MD, MPH, the lead investigator and chair of the Allegheny Health Network Medicine Institute, remarked, “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.” She emphasized the importance of earlier intervention with biologics, which is now a focus in global lupus treatment recommendations.
Patients diagnosed with SLE face serious health risks, including an elevated chance of early mortality and a 50% likelihood of developing irreversible organ damage within five years. This risk is often exacerbated by ongoing disease activity and chronic exposure to corticosteroids. The revised recommendations for SLE treatment in 2025 highlight the importance of achieving DORIS remission and encourage the reduction of corticosteroid use as primary goals in therapy.
Anifrolumab, a first-in-class fully human monoclonal antibody, works by binding to subunit 1 of the type 1 interferon receptor, effectively blocking the activity of type I interferon. While previously available in the US as an intravenous infusion administered by healthcare professionals, the new subcutaneous formulation allows for self-administration by patients. This version received approval in the European Union in December 2025.
Details of the TULIP-SC Trial
The TULIP-SC trial was a multinational, double-blind, placebo-controlled study that involved 220 adult participants aged 18 to 70 with moderate-to-severe SLE despite being on standard therapies such as oral corticosteroids, antimalarial drugs, or immunosuppressants. Participants were randomly assigned to receive either 120 mg of subcutaneous anifrolumab or a placebo, administered via a pre-filled syringe.
The primary endpoint of the trial was the treatment difference in the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at 52 weeks. The interim analysis showed that the primary endpoint was met, with a BICLA response of 59.4% for anifrolumab compared to 43.9% for the placebo group, resulting in a treatment difference of 15.5% (95% confidence interval [CI], 2.3 – 28.6; P = 0.0211).
In the full analysis, which included 367 patients, those treated with anifrolumab demonstrated a higher likelihood of achieving a BICLA response while maintaining lower doses of oral glucocorticoids (≤ 7.5 mg per day) through week 52, at rates of 56.2% compared to 34.0% for the placebo (difference, 22.3%; 95% CI, 12.3 – 32.2; P < 0.0001). Additionally, patients on anifrolumab experienced a reduced time to first sustained BICLA response, with a hazard ratio of 2.2 (95% CI, 1.5 – 3.2; P < 0.0001). At the conclusion of the trial, remission rates based on DORIS criteria and the achievement of a Low Lupus Disease Activity State were significantly higher in the anifrolumab group, with treatment differences of 14.2% (95% CI, 5.6 – 22.8; P = 0.0012) and 14.1% (95% CI, 4.6 – 23.6; P = 0.0038), respectively. Notably, 29% of patients on anifrolumab achieved DORIS remission, while 40.1% attained low disease activity.
Safety Profile and Future Implications
The safety profile for anifrolumab was consistent with previous findings for the intravenous formulation, although the group receiving anifrolumab reported a slightly higher incidence of serious adverse events (11.9% vs 10.4% for placebo). Herpes zoster was observed in 3.8% of participants on anifrolumab compared to 1.1% in the placebo group.
Sharon Barr, executive vice president at AstraZeneca, commented on the implications of the TULIP-SC findings. “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,” she said. “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.”
The results of this trial could mark a significant advancement in the treatment landscape for systemic lupus erythematosus, offering hope for improved patient outcomes and the potential for a shift in therapeutic strategies in line with updated global recommendations.