Therapeutic Approaches for Cutaneous Lupus Erythematosus: a Changing Landscape of Clinical Trials

Abstract: Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease that can occur with or without systemic lupus erythematosus (SLE). To date, there are no specific FDA-approved therapies specifically for CLE. Historically, SLE clinical trials showed promising skin-related outcomes as secondary endpoints; however, these drugs have not received FDA approval specifically for CLE, which limits their availability and insurance coverage for patients with only CLE. Clinical trials for drugs to treat SLE have often utilized primary endpoints such as the SLE Responder Index (SRI) and BILAG-Based Composite Lupus Assessment (BICLA), which are systemic-focused endpoints. With the recent acceptance of Cutaneous LE Disease Area and Severity Index (CLASI) as an endpoint, it can now be used to study response in skin as a primary outcome for clinical trials in LE. The goal of this review paper is to examine the therapeutic use of several existing SLE drugs and new emerging therapies in CLE and their clinical trial and real-world outcomes. Existing SLE drugs such as belimumab and anifrolumab have shown potential promise as a treatment for CLE, and a Phase III CLE clinical trial for anifrolumab is ongoing. Other emerging therapies such as deucravacitinib, litifilimab, and enpatoran have been successful with skin-related endpoints in Phase II CLE trials. A phase II/III CLE clinical trial for litifilimab is ongoing, and phase III trials for enpatoran are planned. As CLASI has become an accepted primary endpoint for clinical trials, drug development is shifting to prioritize cutaneous outcomes and to use endpoints that measure skin-specific effects. This targeted approach represents a fundamental change that may ultimately increase FDA-approved therapies specifically for CLE and expand treatment options for patients with CLE. Keywords: cutaneous lupus erythematosus, CLASI, clinical trials, quinacrine, litifilimab, enpatoran