Lenabasum, a cannabinoid receptor type 2 (CB2) agonist which decreases inflammation, was well tolerated and associated with improved efficacy against dermatomyositis, according to findings from a phase II randomized controlled trial published in The Journal of Investigative Dermatology.
Investigators included adults with a Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) score of 14 or greater, denoting moderate disease, and a history of hydroxychloroquine treatment failure in the study. Participants were randomly assigned 1:1 to receive either placebo or lenabasum 20 mg daily for days 1 through 28, followed by 20 mg twice daily for days 29 through 84. Changes in CDASI score were assessed compared with baseline. Investigators also measured participant quality of life and disease activity using standard measurement tools.
To evaluate safety and tolerability, investigators monitored adverse events, laboratory values, electrocardiogram results, and vital signs. Investigators obtained optional punch biopsies of lesional and nonlesional skin on days 1, 29, and 85 to biomarker and histology assessments. Peripheral blood mononuclear cells (PBMCs) were also obtained at these time points.
Of 22 participants included in the study, the majority were women and the mean age was around 52 years. Most participants in both groups were of White non-Hispanic ethnicity.
Starting at day 43, which was 2 weeks after increasing the lenabasum dose, the change from baseline CDASI score in the lenabasum group was greater than the placebo group (P =.0857) and continued to increase significantly though day 113 (P =.0382). By the end of the study period, 18.2% of patients in the lenabasum group had CDASI of less than14 compared, while all participants in the placebo group had CDASI scores greater than 20 (P =.0351).
There were no serious adverse events reported. All but 1 participant reported at least 1 adverse event. The most common adverse event in the lenabasum group was mild dizziness and in the placebo group was mild or moderate fatigue. There were mild psychiatric adverse events observed in the lenabasum group including daydreaming, abnormal dreams, agitation, depressed mood, and irritability, and in the placebo group there were incidents of anxiety and insomnia. All psychiatric adverse events were short-lived and resolved spontaneously.
Biomarker assessments showed lenabasum was associated with significant reductions in IFN-ß and IFN-y levels at day 85 (P <.05). There were no significant differences for other biomarkers, PBMCs, or cytokine gene expression from skin biopsies between groups.
The study was limited by small sample size, short duration, and lack of correction for multiple comparisons.
“In aggregate, improvement in physician-assessed, patient-reported, and biomarker outcomes suggest clinical benefit of lenabasum in DM patients with refractory skin disease,” the study authors wrote.
Werth VP, Hejazi E, Pena SM, et al. Safety and efficacy of lenabasum, a cannabinoid receptor type 2 agonist, in patients with dermatomyositis with refractory skin disease: A randomized clinical trial. J Invest Dermatol. Published online April 29, 2022. doi:10.1016/j.jid.2022.03.029