Safety and Efficacy of Lenabasum, a Cannabinoid Receptor Type 2 Agonist, in Patients with Dermatomyositis with Refractory Skin Disease: A Randomized Clinical Trial.

BACKGROUND: Treatment options are limited for skin disease in dermatomyositis. Lenabasum is a cannabinoid receptor type 2 agonist that triggers the resolution of inflammation. OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of lenabasum in patients with refractory cutaneous dermatomyositis. DESIGN: This study was a single-center, double-blind, randomized, placebo-controlled phase 2 study conducted from July 2015 to August 2017. POPULATION: The population included subjects aged ≥18 years with at least moderately active dermatomyositis skin activity by Cutaneous Dermatomyositis Disease Area and Severity Index activity ≥ 14 and failure or intolerance to hydroxychloroquine. INTERVENTION: Participants received 20 mg lenabasum daily for 28 days and then 20 mg twice per day for 56 days or placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was a change in Cutaneous Dermatomyositis Disease Area and Severity Index activity. Safety and other secondary efficacy assessments were performed till day 113. RESULTS: A total of 22 subjects were randomized to lenabasum (n = 11) or placebo (n = 11). No serious or severe adverse events were related to lenabasum, and no participants discontinued the study. The adjusted least-squares mean for Cutaneous Dermatomyositis Disease Area and Severity Index activity decreased more for lenabasum, and the difference was significant on day 113 (least-squares mean [standard error] difference = ‒6.5 [3.1], P = 0.038). Numerically greater improvements were seen in multiple secondary efficacy outcomes and biomarkers with lenabasum. CONCLUSION: Lenabasum treatment was well tolerated and was associated with greater improvement in Cutaneous Dermatomyositis Disease Area and Severity Index activity and multiple efficacy outcomes. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, NCT02466243.

Cutaneous Lupus Erythematosus: An Update on Pathogenesis, Diagnosis and Treatment.

Cutaneous lupus erythematosus (CLE) includes a broad range of dermatologic manifestations, which may or may not be associated with systemic disease. Recent studies in this area continue to shape our understanding of this disease and treatment options. Epidemiologic studies have found an incidence of CLE of 4.30 per 100,000, which approaches similar analysis for systemic lupus erythematosus (SLE). Although there have been extensive efforts to define SLE, the classification of CLE and its subgroups remains a challenge. Currently, diagnosis relies on clinical and laboratory findings as well as skin histology. The Cutaneous Lupus Area and Severity Index™ (CLASI™) is a validated measure of disease activity and damage. CLE pathogenesis is multifactorial and includes genetic contributions as well as effects of ultraviolet (UV) light. Immune dysregulation and aberrant cell signaling pathways through cytokine cascades are also implicated. Patient education and avoidance of triggers are key to disease prevention. Antimalarials and topical steroids continue to be the standard of care; however, immunosuppressants, thalidomide analogs and monoclonal antibodies are possible systemic therapies for the treatment of recalcitrant disease.