Interim data suggest early disease control and steroid reduction in routine practice.
Patients with systemic lupus erythematosus (SLE) starting anifrolumab can achieve clinically meaningful disease control within months, with a quarter reaching remission and two-thirds achieving low disease activity by six months, a large real-world cohort study suggests.
The findings come from the interim analysis of the ongoing REVEAL study, a prospective observational cohort following patients treated with the type I interferon receptor antagonist in routine clinical care across 25 tertiary rheumatology centres in Italy.
Results have been published this month in The Lancet Rheumatology.
“Anifrolumab, a fully human monoclonal antibody targeting the type I interferon receptor, represents a novel therapeutic approach for the management of SLE,” the researchers wrote.
“Its efficacy in reducing disease activity and glucocorticoid dependency in patients with moderate-to-severe SLE has previously been shown in randomised controlled trials.
“In 2023, the TULIP-LTE study showed that long-term treatment with anifrolumab, in addition to standard therapy, is associated with a favourable benefit–risk profile in this patient population.”
In the REVEAL study, investigators analysed outcomes from 236 adults with active SLE who initiated anifrolumab between May 2023 and February 2025.
The cohort reflects the heterogeneity typical of real-world lupus populations. Most participants were women (93%) with a median age of 46.9 years and a median disease duration of 11 years.
Nearly half of the patients had irreversible organ damage at baseline. Disease activity at treatment initiation was moderate overall, with a median SLEDAI-2K score of seven. The most common indications for starting anifrolumab were mucocutaneous manifestations (67%) and articular disease (49%). Around 42% of patients received the drug as their first biologic therapy.
At six months, 26% of patients achieved remission according to the Definition of Remission in SLE (DORIS) criteria.
Low disease activity targets were reached even more frequently, with 57% achieving the stricter LLDAS5 definition and 66% reaching the LLDAS overall.
Early improvement was evident well before the six-month mark. At three months, 17% had already achieved remission and more than half were in LLDAS.
Disease activity scores fell rapidly after treatment initiation. Median SLEDAI-2K scores declined from seven at baseline to two by six months, accompanied by significant reductions in physician global assessment scores and SLE-DAS measures. Improvements were detectable as early as one month after the first infusion.
Clinical improvements were mirrored by changes in patient-reported outcomes. Scores for patient global assessment, lupus impact and fatigue improved within the first month and remained better over time, suggesting that early clinical response translated into perceived reductions in disease burden.
Organ-specific responses were particularly notable in the cutaneous and musculoskeletal domains. Among patients with active skin disease or arthritis at baseline, significant reductions in CLASI activity scores and tender and swollen joint counts were recorded within the first month of therapy.
Serological activity also improved, with the proportion of patients showing active serology dropping from 72% at baseline to 57% at one month and 55% at six months.
Steroid exposure declined alongside clinical improvement. The mean daily glucocorticoid dose fell significantly after treatment initiation, and 11% of patients receiving steroids at baseline were completely glucocorticoid-free by six months.
Safety findings were broadly consistent with previous clinical trials. Investigators recorded 108 adverse events over six months, with infections accounting for 77% of these events.
Most of these events were mild, however five serious adverse events led to six hospitalisations, and treatment discontinuation occurred in 8% of patients overall, most commonly due to lack of efficacy or adverse events.
The investigators noted that the rates of remission and low disease activity observed in this real-world cohort appear higher than those reported in randomised trials of anifrolumab.
Differences in baseline disease activity, patient demographics and background therapies may partly explain the discrepancy. The REVEAL cohort had slightly lower baseline disease activity than the pivotal TULIP trials and higher use of concomitant antimalarials and immunosuppressants.
Importantly, the study also highlighted the speed at which therapeutic targets may be achieved in routine care.
“This appears to be the result of both the prompt control of disease activity and the ability to quickly taper glucocorticoid doses,” the researchers wrote.
“This is not surprising if we consider the mechanism of action of the drug and clinical data from randomised controlled trials.
“Indeed, pooled data from TULIP-1 and TULIP-2 studies showed that a greater proportion of patients attained both a British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) and a SRI4 response compared with the placebo group from week eight onwards, including a greater proportion of patients attaining a CLASI-A skin response with anifrolumab versus placebo from the same timepoint.”
However, the researchers cautioned that the observational design and lack of a control group meant the findings should be interpreted carefully, as improvements could partly reflect regression to the mean or natural disease fluctuation.
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In addition, not all participants had reached the six-month follow-up point at the time of analysis.
“Nonetheless, the extent and consistency of improvement across multiple disease activity measures suggest a potential real-world effectiveness of anifrolumab,” they wrote.
The REVEAL study will continue for five years, with ongoing recruitment and extended follow-up expected to provide further insights into the long-term effectiveness and safety of anifrolumab in diverse SLE populations.
“To the best of our knowledge, this is the largest real-world study on the use of anifrolumab in patients with SLE,” the researchers concluded.
“In this study, anifrolumab therapy has proven to be effective in clinical practice, inducing a rapid and meaningful control of extra-renal manifestations while allowing for a significant reduction in glucocorticoid use.
“The expansion of the study population and the extension of the follow-up period will allow for a more accurate definition of medium-term and long-term clinical outcomes, as well as a better characterisation of anifrolumab safety profile.”
