Highlights
Interim analysis from the prospective REVEAL study provides compelling real-world evidence for the use of anifrolumab in systemic lupus erythematosus (SLE). Key highlights include:
- 66% of patients achieved the Lupus Low Disease Activity State (LLDAS) at 6 months.
- 26% of the cohort reached full clinical remission (DORIS criteria) within the first half-year of treatment.
- Rapid clinical response was particularly evident in patients with mucocutaneous (67%) and articular (49%) manifestations.
- Safety data aligned with previous phase 3 trials, though infections were the most frequently reported adverse event.
Introduction: The Evolution of SLE Management
Systemic lupus erythematosus (SLE) remains one of the most challenging autoimmune conditions to manage due to its heterogeneous clinical presentation and unpredictable flare patterns. For decades, the therapeutic mainstay relied heavily on corticosteroids and broad-spectrum immunosuppressants, which, while effective, often carried a significant burden of long-term toxicity. The identification of the Type I interferon (IFN-I) pathway as a central driver in SLE pathogenesis marked a paradigm shift in our understanding of the disease, leading to the development of targeted biologics.
Anifrolumab, a fully human monoclonal antibody that binds to the Type I interferon receptor subunit 1 (IFNAR1), was approved following the success of the TULIP clinical trial program. However, as is common with many breakthrough therapies, a gap exists between the controlled environment of randomized clinical trials (RCTs) and the complexities of routine clinical practice. Real-world evidence is essential to understand how unselected patient populations—often with multiple comorbidities and varied background treatments—respond to this novel therapy. The REVEAL study was designed to bridge this knowledge gap.
The REVEAL Study: Methodology and Design
The REVEAL study is a 5-year, multicentre, prospective observational study conducted across 25 tertiary rheumatology centres in Italy. This pre-specified interim analysis focuses on the first 236 patients recruited between May 2023 and February 2025. Unlike the restrictive inclusion criteria of RCTs, REVEAL enrolled consecutive patients who initiated anifrolumab based on the clinical judgement of their treating rheumatologists and according to Italian regulatory indications.
Eligible participants were required to be at least 18 years old with a diagnosis of SLE fulfilling ACR or EULAR/ACR classification criteria. The study tracked data at baseline, 1 month, 3 months, and 6 months. The primary outcomes were centered on three rigorous clinical milestones:
Clinical Remission
Defined by the Definition of Remission in SLE (DORIS) criteria: a clinical SLEDAI-2K score of 0, a Physician Global Assessment (PGA) score of <0.5, and a stable prednisone-equivalent dose of ≤5 mg/day.
Lupus Low Disease Activity State (LLDAS)
Defined as a SLEDAI-2K ≤4 with no activity in major organ systems, no new disease activity, a PGA ≤1.0, and a prednisone dose ≤7.5 mg/day.
LLDAS5
A more stringent modification of LLDAS requiring a prednisone dose ≤5 mg/day.
Baseline Characteristics: A Real-World Phenotype
The interim cohort consisted of 236 patients, predominantly female (93%) and White (92%), with a median age of 46.9 years. At the time of anifrolumab initiation, the median SLEDAI-2K score was 7, indicating moderate disease activity. The clinical profile of these patients reflected the common “real-world” indications for anifrolumab:
- Mucocutaneous involvement: 67% (157 patients)
- Articular involvement: 49% (116 patients)
This distribution suggests that clinicians are primarily utilizing anifrolumab for patients with refractory skin and joint disease, which are often the manifestations most detrimental to a patient’s quality of life, even if they are not immediately life-threatening.
Results: Early Clinical Response and Efficacy
The findings from the 6-month analysis are highly encouraging for the rheumatology community. Of the 140 patients who reached the 6-month follow-up mark at the time of data cutoff, the response rates were robust:
- LLDAS: 66% (93/140) of patients achieved this state, suggesting that two-thirds of patients can reach a stable, low-activity disease state within six months.
- LLDAS5: 57% (80/140) met this more stringent criteria, highlighting the steroid-sparing potential of anifrolumab.
- Remission: 26% (37/140) achieved full clinical remission according to DORIS criteria.
These figures suggest a rapid onset of action. In the context of SLE, where flares can lead to cumulative organ damage, the ability to achieve LLDAS or remission within 24 weeks is a significant clinical victory. The high rate of LLDAS5 attainment is particularly noteworthy, as reducing daily prednisone to 5 mg or less is a primary goal in modern SLE management to mitigate cardiovascular and metabolic risks.
Safety and Tolerability
Safety is a paramount concern in real-world settings where patients may be more fragile than trial participants. During the 6-month follow-up, 108 adverse events (AEs) were recorded. The majority of these (77%) were infections, which is consistent with the mechanism of action of an IFN-I antagonist. There were five serious adverse events (SAEs) leading to six hospitalizations. While the infection rate warrants vigilance, particularly regarding viral infections like herpes zoster (though specific viral breakdowns were not detailed in this interim report), the overall safety profile appears manageable within routine care.
Expert Commentary: Clinical Implications
The REVEAL interim analysis confirms that the efficacy observed in the TULIP-1 and TULIP-2 trials translates effectively into the “messy” reality of clinical practice. One of the most significant takeaways for clinicians is the high LLDAS attainment rate. In clinical practice, LLDAS has been shown to be as protective as remission against future organ damage, making it a highly pragmatic treatment target.
The heavy representation of mucocutaneous and articular phenotypes in this study reinforces anifrolumab’s niche. While further data are needed regarding its use in active lupus nephritis—a population currently being studied in separate trials—the REVEAL data solidify anifrolumab as a potent option for the most common and persistent manifestations of SLE. The rapid response observed also suggests that clinicians do not need to wait for a year to determine if the drug is working; significant improvements are often visible by the 3-to-6-month window.
However, the study is not without limitations. As an observational study, it lacks a control group, and the 6-month timeframe is relatively short for a chronic disease. Furthermore, the cohort is predominantly White, which may limit generalizability to other ethnic groups who often experience more severe SLE phenotypes. As the REVEAL study continues toward its 5-year goal, longer-term data on organ damage accrual and steroid withdrawal will be vital.
Conclusion
The interim analysis of the REVEAL study provides a reassuring and positive outlook for anifrolumab in the real-world treatment of SLE. With 66% of patients reaching LLDAS and over a quarter achieving remission within six months, the drug demonstrates a rapid and meaningful clinical impact. For the clinician, these data support the early introduction of anifrolumab in patients with active mucocutaneous and articular disease, offering a clear path toward steroid reduction and disease stabilization.
Funding and Registration
The REVEAL study received no specific funding for this interim analysis. It is registered with ClinicalTrials.gov (NCT07215754) and the Italian Medicines Agency (AIFA, ID number 247). Recruitment is ongoing to reach long-term observational goals.
References
Tani C, Cardelli C, Moroni L, et al. Patient profiles and early response in patients with systemic lupus erythematosus initiating anifrolumab: interim analysis from the ongoing multicentre observational REVEAL study. Lancet Rheumatol. 2026 Feb 5. doi: 10.1016/S2665-9913(25)00316-9.
