Apremilast effective in treating Recalcitrant Cutaneous Dermatomyositis

Cutaneous disease in dermatomyositis has no standardized treatment approach and so presents a challenging task for patients and clinicians.

A study was conducted to study the efficacy and safety of apremilast as add-on therapy in patients with recalcitrant cutaneous dermatomyositis.

This phase 2a, open-label, single-arm nonrandomized controlled trial was conducted at a single centre from June 2018 to June 2021. Participants were 8 patients with recalcitrant cutaneous dermatomyositis, defined by a cutaneous disease activity severity index (CDASI) score greater than 5 despite treatment with steroids, steroid-sparing agents, or both. Data were analyzed from June 2018 to June 2021.

The primary outcome was the overall response rate (ORR) at 3 months. Key secondary outcomes were the safety and toxicity of apremilast and the durability of response at 6 months. The CDASI, muscle score, dermatology life quality index (DLQI), and depression assessments were performed at baseline and regularly until month 7. Skin biopsies were performed at baseline and 3 months after apremilast (defined as 3 months into active apremilast therapy) and tested for gene expression profiling and immunohistochemical stains. Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0.

Results:

• Among 8 patients with recalcitrant cutaneous dermatomyositis, a response was found at 3 months after apremilast among 7 patients (ORR, 87.5%).
• The mean (SD) decrease in CDASI was 12.9 (6.3) points at 3 months (P < .001).
• Apremilast was well tolerated, with no grade 3 or higher adverse events. Sequencing of RNA was performed on skin biopsies taken from 7 patients at baseline and at 3 months after therapy. Appropriate negative (ie, no primary antibody) and positive (ie, tonsil and spleen) controls were stained in parallel with each set of slides studied.
• Of 39 076 expressed genes, there were 195 whose expression changed 2-fold or more at P < .01 (123 downregulated and 72 upregulated genes).
• Gene set enrichment analysis identified 13 pathways in which apremilast was associated with downregulated expression, notably signal transducers and activators of transcription 1 (STAT1), STAT3, interleukin 4 (IL-4), IL-6, IL-12, IL-23, interferon γ (IFNγ), and tumor necrosis factor α (TNFα) pathways.
• In immunohistochemical staining, there was a mean (SD) decrease in phosphorylation levels STAT1 (22.3% [28.3%] positive cells) and STAT3 (13.4% [11.6%] positive cells) at the protein level, a downstream signalling pathway for the downregulated cytokines.

These findings suggest that apremilast was a safe and efficacious add-on treatment in recalcitrant dermatomyositis, with an overall response rate of 87.5% and associations with downregulation of multiple inflammatory pathways.

Reference:

Bitar C, Ninh T, Brag K, et al. Apremilast in Recalcitrant Cutaneous Dermatomyositis: A Nonrandomized Controlled Trial. JAMA Dermatol. Published online October 05, 2022. doi:10.1001/jamadermatol.2022.3917

Keywords:

Bitar C, Ninh T, Brag K, Apremilast, Recalcitrant, Cutaneous, Dermatomyositis, Nonrandomized Controlled Trial, JAMA Dermatology