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Add-on apremilast may improve recalcitrant dermatomyositis

Presented By
Prof. Carole Bitar, Tulane University School of Medicine, USA
Presented by
Carole Bitar
AAD 2022
Phase 2
With an overall response rate of 87.5%, apremilast demonstrated efficacy as an add-on treatment for recalcitrant dermatomyositis without raising safety concerns in a small phase 2a trial. An additional transcriptome analysis revealed a downregulation of key signalling pathways by apremilast.

Dermatomyositis is 1 of the 3 main types of idiopathic inflammatory myopathies. Most patients present with typical skin signs and half of them also suffer from muscle weakness [1,2]. There is a demand for more efficacious treatment options because even with extensive use of current therapies, a great proportion of patients is not adequately controlled [3].

A phase 2a open-label trial (NCT03529955) investigated the phosphodiesterase-4 inhibitor apremilast as an add-on therapy for recalcitrant cutaneous dermatomyositis [4]. The study included 8 patients who met the inclusion criteria of Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) ≥5 while on treatment with a stable dose for 1 month, age 18­–75 years, and appropriate cancer screening. “All patients were heavily pre-treated,” Prof. Carole Bitar (Tulane University School of Medicine, LA, USA) pointed out. For 6 months, the study participants received twice-daily 30 mg of apremilast on top of their regular therapy with steroids and/or steroid-sparing drugs. Participants were monitored for 7 months on parameters such as CDASI and dermatology life quality index (DLQI), and skin biopsies were obtained at baseline and at 3 months for further genetical and immunohistochemical investigation.

After 12 weeks of treatment, the participants showed a general response rate of 87.5%. Prof. Bitar explained that a continuous decrease in CDASI score was observed over time of treatment. The results established a significant 12.9-point mean drop in CDASI (P<0.05). “There was also relevant improvement in DLQI,” Prof. Bitar said.

Only grade 1–2 side effects according to the Common Terminology Criteria for Adverse Events (version 5.0) were reported. The most common were headache (87.5%), nausea (62.5%), and diarrhoea (50%).

The researchers also wanted to find out why apremilast influences dermatomyositis. To gain further insight, the researchers looked at the results of RNA sequencing, specifically of ≥2-fold transcriptome changes (P<0.01). They identified 195 affected genes, of which 123 were downregulated and 72 upregulated through apremilast. A gene set enrichment analysis detected 13 pathways that were downregulated by the apremilast treatment. Of note, these included IL-6, IL-12, IL-23, as well as STAT-11 and STAT-3. Inhibition of JAK/STAT signalling was corroborated by the immunohistochemical assessment.

In summary, the add-on treatment of recalcitrant dermatomyositis with apremilast showed promising benefits and was well tolerated.

    1. Bitar C, et al. JAAD Case Rep. 2019;5(2):191–194.

    2. Piguet V, Choy E. Br J Dermatol. 2018;179(6):1233–1234.

    3. Wolstencroft PW, et al. JAMA Dermatol. 2018;154(1):44–51.

    4. Bitar C, et al. Apremilast induces high response rates in recalcitrant dermatomyositis with downregulation of multiple inflammatory pathways: results of a phase 2a open-label study. S026, AAD 2022 Annual Meeting, 25–29 March, Boston, MA, USA.


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