NEW YORK — If not doing so already, dermatologists should participate, if not lead the care of cutaneous lupus erythematosus (CLE) now that several therapies appear to be moving toward regulatory approval, according to an expert in this field.

Although nothing beyond hydroxychloroquine is yet approved for CLE, the “explosion of biologics” that has already increased options for systemic lupus erythematosus (SLE) are among several therapies in late stages of testing for CLE, reported Joseph F. Merola, MD, chair in the Department of Dermatology at the University of Texas Southwestern Medical School, Dallas.

Whether CLE is an isolated condition or a part of a systemic disease, Merola is concerned that dermatologists often refer cases to avoid SLE, a disease for which many feel unqualified to treat. He said that this orientation should change with the availability of more treatment options and a better understanding of clinical targets.

Dermatologists Should ‘Own’ Cutaneous Lupus

Whether CLE is an isolated entity or occurs in the context of SLE, “we as dermatologists can and should own this disease,” Merola said at the Sixth Inflammatory Skin Disease Summit on November 13.

CLE is the first sign of SLE in about 30% of cases, but not all cases of CLE progress to systemic involvement, Merola said. In fact, CLE is about as prevalent as SLE, but patients with both or those who progress from one to the other “still need therapy for the skin,” he noted.

With limited treatment options for CLE, dermatologists, particularly those outside of tertiary centers, are often resistant to being involved with the care of these patients, but this should change, Merola noted. The difference now is the “incredibly exciting data” being generated by a “strong” pipeline of new therapies targeted specifically at CLE.

This is in part because of progress in understanding the underlying pathophysiology of CLE, but Merola also said that CLE trials have been thwarted by a lack of consensus about clinically meaningful endpoints. He outlined the problem and potential solutions in a 2021 paper he co-authored on highlighting CLE outcome measures.

Subsequent publications by Merola and others, including Victoria Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, led to trial designs and endpoints that the FDA and other regulatory agencies have accepted for testing treatments.

“We are in a new era,” said Merola, referring to phase 2 and 3 trials that are generating encouraging degrees of efficacy with acceptable safety.

Much of this development involves biologics already approved for SLE. For example, belimumab, a monoclonal antibody targeting the B-lymphocyte stimulator, approved for SLE in 2011, has shown clinically meaningful improvements in the cutaneous manifestations of CLE alone. It is an attractive candidate for CLE even if no pivotal trial has yet been completed.

Skin improvements were observed in the phase 3 trial of anifrolumab, which led to FDA approval for SLE after it was published in 2020, Merola said. A phase 3 trial of efficacy specific to CLE with this agent, which blocks the type 1 interferon receptor subunit, was initiated in 2024 and top-line results are expected by the end of 2026.

New Therapeutic Targets Are Showing Promise

Litifilimab, a monoclonal antibody that binds to blood dendritic cell antigen 2, is not yet approved for SLE, but it also shares promise for CLE based on activity against skin involvement in a phase 2 trial, Merola reported.

Enpatoran, an oral agent that inhibits Toll-like receptors 7 and 8 to reduce inflammation and autoantibody activity, is yet another experimental drug that has shown promising degrees of activity against both SLE and CLE in phase 2 trials.

Positive results for CLE with deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor approved for moderate-to-severe psoriasis, were first reported in several case reports. This activity has now been supported by initial 16-week results from a 52-week phase 2 study presented as a late-breaker at the American Academy of Dermatology (AAD) 2025 Annual Meeting.

The endpoints being applied in randomized CLE trials, such as the Cutaneous Lupus Erythematosus Disease Areas and Severity Index, investigator-based assessments, and patient-reported outcomes, including pain and itch, are typically used in combination, Merola reported.

Even if it is too early to conclude anything about the relative promise of these or other agents on the long list drugs in the pipeline for CLE overall and for its subtypes, such as discoid lupus erythematosus, they promise to transform care of the skin, according to Merola.

CLE, a potentially disfiguring condition that easily rivals other inflammatory skin disease for its adverse impact on quality of life, appears to be on a path toward meaningful levels of control even among those with severe involvement. Whether patients with lupus have CLE alone or SLE with cutaneous involvement, the new therapies specific to the skin provide a strong rationale for dermatologists to be a part of the diagnosis and treatment of these conditions even if a multidisciplinary team is required.

“I am not saying that every dermatologist should try to treat outside their zone of comfort, but we can collaborate with our rheumatologist colleagues to improve the outcomes of these patients,” Merola said.

When contacted for her perspective, Werth said, “I totally agree” with the principle that lupus is a disease which will benefit from the participation of dermatologists. At her center, this has already occurred.

“We now have a large group of medical dermatologists, some of whom are internists and dermatologists, who treat patients with cutaneous lupus and other autoimmune and complex medical skin diseases,” Werth told Medscape Medical News. Currently, “the referral patterns for CLE typically include dermatologists who specialize in this area,” but she predicts that more effective targeted therapies should draw more dermatologists to this field.

“Dermatologists have a lot to offer and as better treatments become available should embrace treatment of cutaneous lupus,” she said.

Merola reported having financial relationships with AbbVie, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavent, Eli Lilly, Galderma, Incyte, Janssen, Moonlake, Novartis, Oruka, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB. Werth reported having no potential conflicts of interest.