Emerging Treatments for CLE Highlighted at Fall Clinical

Cutaneous lupus erythematosus (CLE) patients often face long treatment timelines, drug toxicity, and misdiagnoses, but recent advances in mechanism-based agents mark a significant step forward, Lauren Graham, MD, PhD, and Alisa Femia, MD, said during a presentation at the 2025 Fall Clinical Dermatology Conference.

Drs. Graham and Femia outlined evolving diagnostic strategies and promising therapies for CLE during “Unlocking Possibilities: Emerging Therapies for Cutaneous Lupus Erythematosus.”

Accurate diagnosis remains a key challenge in CLE, particularly when distinguishing malar rash of lupus from rosacea, contact dermatitis, or dermatomyositis. Dr. Graham presented comparative facial images to highlight subtle diagnostic features. Malar rash, she noted, is characterized by patchy erythema with sparing of the nasolabial folds, often with hemorrhagic crusting or frontal hairline alopecia. Rosacea, meanwhile, involves papulopustular lesions with involvement of the nasolabial folds and typically lacking systemic symptoms. Dermatomyositis facial rash presents with midfacial erythema without typical malar distribution.

While biopsies can support diagnosis, they rarely distinguish CLE from mimickers like seborrheic dermatitis or atopic dermatitis. Therefore, photo-distribution patterns, sparing characteristics, and symptom context are critical.

“The key is knowing the common anatomic distributions and being cautious not to attribute every eruption in (systemic lupus erythematosus) patient to lupus itself,” said Dr. Femia.

Subacute CLE (SCLE) typically presents as annular or polycyclic plaques in sun-exposed areas but may also mimic other dermatoses. SCLE can be drug-induced, and reviewing medication history is essential.

Discoid lupus erythematosus (DLE) often involves scarring alopecia and pigmentary changes. Early recognition—before scarring sets in—is crucial.

“By the time they reach us, it’s often too late,” said Dr. Graham. “We need to catch DLE at the erythematous, scaly patch stage.”

Traditional treatments, such as hydroxychloroquine, methotrexate, and mycophenolate mofetil, remain first-line, but have notable drawbacks including delayed onset and tolerability issues.

Dr. Graham and Dr. Femia summarized three emerging treatment options.

Anifrolumab is a Type I interfero receptor agonist that is approved for treating SLE and is often used off-label for CLE. It has displayed ≥50% reduction in CLASI scores in clinical trials. It is administered via IV infusion every 4 weeks. There is an increased risk of herpes zoster, so the shingles vaccination is advised.

"This drug has changed my life," a patient told Dr. Graham.

Deucravacitinib, an oral selective TYK2 inhibitor approved for moderate-to-severe plaque psoriasis, is currently in phase 3 trials for SLE and CLE. It has no black box warning and is well-tolerated. In trials, all evaluated doses showed >50% CLASI reduction.

Litifilimab is an anti–BDCA2 monoclonal antibody targeting plasmacytoid dendritic cells, reducing type I interferon production. Administered via subcutaneous injection every 4 weeks, it is in phase 3 trials for SCLE and DLE. It has displayed improvement in erythema and scaling by week 16, and it may offer a non-immunosuppressive option for patients with depression or thrombosis risk (eg, unsuitable for thalidomide or lenalidomide).

Drs. Graham and Femia proposed a revised treatment ladder for CLE:

• Place deucravacitinib and anifrolumab alongside or ahead of methotrexate in patients with moderate-to-severe disease.
• Use mechanism-based matching: Consider anifrolumab in patients with high interferon signature, and deucravacitinib for patients preferring oral therapy or with contraindications to IV.

“We don’t see a reason to delay these newer agents after HCQ failure. Their tolerability and efficacy make them front-line considerations,” Dr. Graham said.