Anifrolumab Achieves DORIS Remission, LLDAS in Real-World SLE Practice

Anifrolumab (Saphnelo) appears to be holding up in real-world data - in a 12-month interim analysis of the multinational ASTER observational study (NCT05637112) — enrolling adults with systemic lupus erythematosus (SLE) treated with anifrolumab in routine clinical practice across 530 patients — 43.0% (95% CI, 34.5–51.8%) attained DORIS remission and 74.1% (95% CI, 65.8–81.2%) attained Lupus Low Disease Activity State (LLDAS) during the follow-up period, both rates higher than those observed in the randomized TULIP clinical trial program.^1,2

Sustained responses were also observed: 25.9% of patients spent ≥2 consecutive visits in DORIS remission and 47.4% in LLDAS — clinically meaningful thresholds given evidence that sustained DORIS or LLDAS attainment lasting longer than 3 months is protective against irreversible organ damage accrual.¹ A pre-treatment analysis found that patients who went on to achieve DORIS remission had lower baseline SLEDAI-2K scores (mean [standard deviation (SD)], 6.6 [SD, 3.5] vs 8.3 [SD, 4.0]) and lower pre-treatment glucocorticoid dosage among GC users (6.4 [SD, 4.9] mg/day vs 11.6 [SD, 9.5] mg/day) compared with those who did not — a finding with direct implications for when anifrolumab should be introduced in the treatment course. Serious adverse events were observed in 8.3% of patients in the interim safety population, with adverse drug reactions in 10.2%.¹

The results were presented as an oral abstract at the European Alliance of Associations for Rheumatology (EULAR), held in London in June. Rheumatology Live caught up with first author Marta Mosca, MD, PhD, Professor of Rheumatology at the University of Pisa and Head of the Rheumatology Unit at the Azienda Ospedaliero Universitaria Pisana, Pisa, Italy, to discuss what the ASTER data tell us about anifrolumab's real-world performance, the role of timing in achieving remission, and what the results mean for how rheumatologists should be thinking about glucocorticoid reduction as a primary treatment goal in SLE.

RheumatologyLive: What does the ASTER interim data tell you about whether anifrolumab is living up to its promise in the real world, and where do you still have questions?

Marta Mosca, MD, PhD: The ASTER interim data is encouraging because it shows that what we observed in the clinical trial programme is translating into routine clinical practice. In this 12-month interim analysis, 43% of patients achieved DORIS remission and 74.1% reached Lupus Low Disease Activity State (LLDAS), which tells us that these are not just research endpoints - they are achievable treatment goals in clinical practice.Further, ourresults suggestanifrolumab treatment in real-world clinical practice can support sustained DORIS remission and LLDAS attainment

What I find especially notable is that ASTER reflects everyday clinical practice, where patients are often more heterogeneous and clinically complex than those enrolled in randomized trials. It is important to note that ASTER is an ongoing observational, cohort study, and the longer-term follow-up will help us better understand how durable these outcomes are over time and whether these remission rates can be sustained over the longer term and how they translate into reduced organ damage over time.

How has anifrolumab's availability changed the conversation you have with patients and colleagues about what remission in SLE should actually look like?

Mosca: I think anifrolumab has helped change the conversation from simply managing disease activity to aiming for remission whenever possible. For many years, remission in SLE was viewed as aspirational.Today, we can have a different conversation with patients, one that focuses on achieving sustained disease control while aiming to reduce reliance on glucocorticoids.

DORIS remission and LLDAS have become practical treatment goals because they give us objective targets to work toward, however the recent treatment recommendations from ACR and EULAR now reinforce this treat-to-target approach, emphasizing reduced glucocorticoid use and earlier intervention with biologic therapies. That represents a significant shift in expectations for both physicians and patients.

The ASTER data suggest that patients who go on to achieve remission tend to have lower disease activity and lower glucocorticoid doses at the time anifrolumab is started. What does that tell you about timing — and is there a risk that anifrolumab is being added too late in some patients' disease course?

Mosca: The findings reinforce the importance of timing. Patients who start anifrolumab with lower disease activity and lower glucocorticoid requirements appear more likely to achieve remission, supporting the principle of earlier intervention and raising an important question about whether some patients are still being escalated too late which is in line withcurrent ACR and EULAR treatment recommendations which advocate for earlier use of biologic therapies alongside glucocorticoid tapering, with remission as the treatment target.

Long-term glucocorticoid use is a well-established driver of irreversible and preventable organ damage in SLE. Rather than waiting until disease becomes more difficult to control, or patients have accumulated damage, these data support introducing effective therapies earlier when there is a greater opportunity to achieve sustained remission, minimize cumulative glucocorticoid exposure, and improve long-term outcomes.

What are you seeing in real-world practice in terms of whether anifrolumab is actually allowing patients to get off or meaningfully reduce steroids, and how central is that to how you use it?

Mosca: Reducing glucocorticoid exposure is one of the central goals of modern lupus management because we know that prolonged glucocorticoid use is a well-established driver of irreversible and preventable organ damage in SLE.

What is encouraging is that we're seeing consistent evidence, from randomized clinical trials, post hoc analyses, and now real-world studies, that anifrolumab can support glucocorticoid reduction while maintaining disease control. For me, that's clinically meaningful because remission isn't simply about achieving low disease activity; it's about doing so with the lowest possible glucocorticoid burden.

For me, glucocorticoid reduction is not a secondary benefit of anifrolumab—it is one of the clearest signs that we are improving care in a way that is safer and more sustainable for patients. If we can control disease activity, help patients taper steroids, and potentially reduce future organ damage, that's an important step toward improving long-term outcomes.

As the field moves toward more precision approaches in SLE, how do you think about patient selection — and do you expect that biomarker-guided prescribing will eventually change who gets anifrolumab and who gets something else?

Mosca: I think we are moving toward a future where biomarkers will help us make more tailored treatment decisions, but we are not quite there yet. Today, SLE remains a highly heterogeneous disease, and we still need therapies that have demonstrated benefit across a broad range of patients.

Anifrolumab has shown consistent efficacy in both clinical trials and now in real-world practice, including helping patients achieve remission while reducing glucocorticoid exposure. The ASTER data reinforce that these goals are achievable outside the clinical trial setting and support the shift toward earlier biologic intervention, as reflected in current ACR and EULAR recommendations.

As our understanding of disease biology continues to grow, biomarkers will likely help us identify which patients are most likely to benefit from specific therapies. But the broader goal won’t change – getting patients into sustained remission earlier, reducing steroid exposure, and ultimately preventing irreversible organ damage.

Mosca;s disclosures include Abbvie, AstraZeneca, Biogen, BMS, GSK, Lilly, Moltenyi, Novartis, Otsuka, Roche, UCB.

References

1. Mosca M, Parodis I, Weinmann-Menke J, et al. DORIS remission and LLDAS attainment after up to 12 months of real-world anifrolumab treatment: interim results from the ASTER study [abstract OP0219]. Ann Rheum Dis. 2026;85(suppl 1). doi:10.1136/annrheumdis-2026-eular.B.1240

2. Golder V, Kandane-Rathnayake R, Huq M, et al. Association of sustained lupus low disease activity state with improved outcomes in systemic lupus erythematosus: a multinational prospective cohort study. Lancet Rheumatol. 2024;6(8):e528–e536. doi:10.1016/S2665-9913(24)00121-8