Dear Editors, Cutaneous lupus erythematosus (CLE) encompasses a spectrum of manifestations that may occur independently or in association with systemic LE (SLE). CLE includes acute (ACLE), subacute (SCLE), and chronic forms such as discoid LE (DLE), chilblain lupus, and lupus panniculitis (LP), all sharing a common pathogenesis involving type I interferon (IFN) dysregulation.1, 2 Despite its potential for disfigurement and quality-of-life impairment, CLE remains difficult to treat. Most therapies were developed for systemic disease, are used off-label in CLE, and are often slow-acting, with limited efficacy, and potential for serious adverse effects (AEs).3, 4 In 2022, the European Medicines Agency approved anifrolumab, a monoclonal antibody targeting the type I IFN receptor, for moderate-to-severe SLE. While post-hoc analyses of pivotal trials (TULIP-1 and TULIP-2) showed significant reductions in cutaneous activity, its efficacy in CLE subtypes remains poorly defined.5, 6 We report our experience with 4 patients with CLE treated with anifrolumab (300 mg i.v. every 4 weeks) after failure of a median of 6.5 prior therapies (range 2–13) due to lack of efficacy or tolerance, including antimalarials, immunosuppressants, and belimumab (Table 1). HCQb (1 mo), CQ (3 y), QC (1 y) MTX (3 y), PDN (3 y), BEL (5 mo), MP (pulses x5) Total: 7 HCQ (8 y), QC (1 y) Total: 2 MMF (10 y), BEL (2 y), RTXb (1 y), TAC (8 y), AZAb (1 y), QCb (1 y), CQb (1 y), HCQb (6 mo), CYC (pulses x12), NIFb (9 mo), PDN (19 y), MP (pulses x3), IVIgb (pulses x 1) Total: 13 HCQ (9 y), PDN (9 y), CQ (2 mo), MTX (6 y), QC (1 y), BEL (1 y) Total: 6 Case 1 was a 39-year-old woman with isolated LP of 4 years’ duration affecting both arms, highly painful and disabling, with frequent flares requiring methylprednisolone pulses. Anifrolumab was added to chloroquine, methotrexate and prednisone (15 mg/day). After 1 month, CLASI-A improved by 67% (Figure 1) and DLQI by 65%. A mild flare after the third dose during corticosteroid tapering (5 mg/day) was resolved by increasing prednisone and methotrexate. After the fourth dose, prednisone was tapered to 7.5 mg/day, with final CLASI-A and DLQI improvements of 67% and 62%. Case 2 was a 38-year-old woman with longstanding facial and scalp DLE, without systemic involvement and on hydroxychloroquine. Following initiation of anifrolumab, she showed an 81% improvement in CLASI-A and 76% in DLQI after 1 month, exceeding 90% improvements by 3 months (Figure 1). Case 3 was a 39-year-old woman with a 26-year history of SLE (hematologic, musculoskeletal, pleural and neurologic involvement, currently inactive) and refractory generalized DLE. After 1 month of anifrolumab and prednisone 5 mg/day, CLASI-A improved by 97% and DLQI by 89%. Complete cutaneous response (CLASI-A 0) was achieved after 5 months (Figure 2). Case 4 was a 52-year-old man with 9-year SLE, without organ involvement or cytopenias, but poorly controlled SCLE on trunk and limbs. After 1 month of anifrolumab combined with hydroxychloroquine and methotrexate, CLASI-A and DLQI improved by 67% and DLQI by 50%, reaching 76% and 100% at 2 months. All patients achieved ≥ 50% CLASI-A reduction within the first month. Median CLASI-A and DLQI improvements at last follow-up were 85% (range 67%–100%) and 90% (range 62%–100%), respectively. No serious AEs occurred; only a mild respiratory infection and a localized HSV-1 reactivation. To contextualize our observations, we reviewed real-world studies on anifrolumab in CLE published up to March 28, 2025 (online supplementary Table S1). We identified 37 articles, 16 single-patient case reports and 21 studies with ≥ 2 patients, describing 152 cases (88.2% women; median age 42) with one or more CLE subtypes, mainly DLE (58%), SCLE (36%), and ACLE (18%); 94% also fulfilling SLE criteria. Before anifrolumab, patients had received a median of 6 systemic treatments (range 2–14), most commonly hydroxychloroquine (91%), methotrexate (60%), corticosteroids (57%), mycophenolate mofetil (53%), and belimumab (49%). Of the 152 patients reviewed, 114 had CLASI-A data and 38 were assessed clinically. Among those with CLASI-A data, 97.4% achieved ≥ 50% score reduction, with 59% reaching CLASI-A 0. Among clinically assessed patients, 60.5% were considered complete responders and 39.5% partial responders. Most responses occurred rapidly, with a median time to partial response of 1 month (range 0.5–5), peak response by 4 months (range 1–8) and median follow-up of 5 months (range 2–20). Interestingly, corticosteroid tapering was reported in nearly half of cases. Anifrolumab demonstrated a favorable safety profile, with 48 AEs (mostly mild infections) reported in 39 patients and discontinuation in 4. Relapses were rare (n = 4) and mainly occurred after treatment interruption or corticosteroid tapering. In conclusion, anifrolumab is an effective and well-tolerated option for multiple CLE subtypes, with a rapid onset of action that may help prevent irreversible damage such as scarring. Its potential corticosteroid-sparing effect is especially relevant in patients with comorbidities or intolerance.7, 8 Dedicated trials with CLE as a primary endpoint, such as the ongoing LAVENDER study (NCT06015737), are essential to validate these findings.9 Future research should focus on identifying predictors of response, refining its role within CLE-specific therapeutic algorithms, and developing optimized treatment strategies.10 None. 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Martínez‐Sernández et al. (Thu,) studied this question.