A new review of discoid lupus erythematosus, or DLE, covers established care and recent biologic and small-molecule treatments for resistant disease. It describes anifrolumab as the targeted agent with the most consistent reported skin benefit, while the WILLOW trial of enpatoran reported higher skin-response proportions than placebo at week 16.
This was a narrative synthesis, not a new treatment trial. The authors searched English-language articles in PubMed, Google Scholar, Web of Science and Scopus published from 1990 through October 2025. They prioritized recent clinical trials, consensus guidelines and high-quality reviews, screened reference lists for additional studies, and included 84 articles.
Treatment still starts with the basics
For localized DLE, treatment begins with photoprotection and topical anti-inflammatory options. The review lists topical corticosteroids and calcineurin inhibitors as first-line choices. Antimalarial therapy is the first-line systemic treatment.
Hydroxychloroquine, or HCQ, is described as the systemic-treatment cornerstone for active DLE. The review says it is typically prescribed at no more than 5 milligrams per kilogram of actual body weight per day.
Yet nearly half of patients experience disease that persists or returns despite standard treatment. For disease that remains resistant, systemic immunosuppressants such as methotrexate and mycophenolate mofetil may be added, but adverse effects and monitoring requirements can limit their use.
The strongest signals are coming from targeted drugs
Among the targeted medicines discussed, anifrolumab had the most consistent reported cutaneous benefit. Multiple studies reported more than 50% improvement on CLASI, a score used to track skin-disease activity and response. Belimumab's benefit was more modest and less consistent, mainly in systemic disease. In the reviewed literature, improvement in discoid lesions was typically seen within 20 weeks and maintained through one year.
The review also highlights litifilimab and daxdilimab. Litifilimab yielded statistically significant reductions in CLASI-A at 16 weeks in a phase 2 trial, with phase 3 studies under way. Daxdilimab produced similar CLASI improvements in early studies, leaving its evidence base at an earlier stage.
One of the sharper signals came from WILLOW, a trial of approximately 100 patients. At week 16, 91% of patients receiving enpatoran achieved a CLASI-50 response, meaning a 50% improvement in the score, compared with 39% in the placebo group. A response defined as more than 70% improvement was reported in 61% of the enpatoran group and 12% of the placebo group. The reported P value was 0.0002, although the review says the sample size was approximate and confidence intervals were not reported.
Promising results do not settle the clinical questions
The review's evidence base mixes DLE, broader cutaneous lupus and systemic lupus populations, along with different study designs. That matters because results from systemic or broader cutaneous disease may not apply directly to people with isolated DLE. The review presents a treatment landscape, not a head-to-head comparison showing that one therapy is superior.
JAK inhibitors illustrate the uncertainty. Controlled evidence for these drugs in DLE remains limited: baricitinib failed to meet a primary endpoint in systemic lupus, while topical R333 did not demonstrate robust efficacy in DLE. The review therefore does not establish a role for these agents in DLE.
Short-term CLASI activity improvements also leave open whether treatment changes the damage left by disease. The authors recommend moving beyond activity scores by adding structural-damage measures and longer follow-up to assess disease modification.
Procedures may have a supporting role
For scarring or lesions that remain difficult to control, procedural treatments may complement medical therapy. The review notes that pulsed dye laser was tried in recalcitrant DLE and was observed to produce clinical improvement over 12 weeks.
The article states that it received no funding or sponsorship for publication and that no new human or animal studies were conducted. No datasets were generated or analyzed. The review disclosed consulting fees for Matthew D. Vesely and Jeffrey R. Gehlhausen, as well as research grants for Gehlhausen; the other listed authors reported no conflicts.
Paper data and sources
Original title: Modern Therapies for Discoid Lupus Erythematosus: A Narrative Review.
Authors: Anshu Jonnalagadda, Rhys L Richmond, Gaurav N Pathak et al.
Journal/Repository: Dermatology and therapy
Status: Peer-reviewed
First online: 2026-08-21
DOI: 10.1007/s13555-026-01888-7
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