New Therapies on Horizon as Science of CLE Advances

Over the past decade, advances in scientists’ understanding of cutaneous lupus erythematosus (CLE) have shed light on the condition’s drivers and set the stage for potential treatments, according to a new review.

The investigators discussed the latest findings and what they mean for patients with CLE in an article in Journal of Autoimmunity.

People with CLE experience recurrent photosensitive skin lesions, and flares can lead to missed work, lower quality of life, scarring, and alopecia. The condition is often associated with systemic lupus erythematosus (SLE), although the authors said it can also be a stand-alone condition. About 70% of people with SLE have cutaneous involvement, and about 20% of people with primary CLE will eventually develop SLE, they said

“While connections between systemic and cutaneous lupus are being identified, definitive mechanistic links have remained elusive, and differences between primary and SLE-associated CLE are not well understood,” the authors wrote, adding that CLE lesions likely develop in a “pro-inflammatory epidermis, conditioned by excess type I interferon (IFN) production to undergo increased cell death and inflammatory cytokine production after UV light exposure.”

Patients with high levels of antinuclear antibodies but without autoimmune disease have a similar inflammatory disposition, they noted. Evidence of CLE is found even in patients’ nonlesional skin; the skin has increased innate immune cell infiltration and plasmacytoid dendritic cells, they said.

“Once the inflammatory cycle begins, lesional infiltration by numerous other cell populations ensues, including IFN-educated T cells,” they wrote.

They noted the 3 main subtypes of CLE: chronic, acute, and sub-acute. Most cases (75%) fall into the chronic subtype, and the investigators said it is not clear what drives the differences in subtypes.

At present, there are no FDA-approved therapies to treat CLE, the authors said. In the absence of CLE-specific therapies, drugs approved for other inflammatory conditions or for SLE can be used. Antimalarial drugs appear to lead to responses in about half of the patients prescribed them, they noted.

Several trials are underway that could soon change the standard of care for CLE. The TULIP trials of anifrolumab (Saphnelo) have shown that the monoclonal antibody led to significant improvement in skin activity. The drug works by blocking type I IFN signaling. Therapies that target the Janus kinase and signal transducer and activator of transcription pathways can also be used to block type I IFNs, the study authors wrote. Other potential therapeutic avenues include targeting blood DC antigen 2 and lymphocyte transcription factors, they said.

Although the investigators said there is reason to be optimistic that more therapeutic options will soon arrive, they said it is important research continue to the point where early, personalized interventions are possible.

“Continued research into mechanisms of CLE is needed so that beyond drug discovery, we will understand how to use the right drugs in the right patients to ameliorate and prevent CLE,” they concluded.

Reference
Maz MP, Martens JWS, Hannoudi A, Reddy AL, Hile GA, Kahlenberg JM. Recent advances in cutaneous lupus. J Autoimmun. Published online July 17, 2022. doi:10.1016/j.jaut.2022.102865