Dermatomyositis (DM) is a severe autoimmune connective tissue disease in which patients routinely endure prolonged courses of systemic treatments that are associated with significant toxicity for their skin disease. Although over 60,000 individuals have DM in the U.S., the majority of whom have skin findings, there have been no prospective studies of treatments for the many patients with skin predominant disease. The goal of this proposal is to initiate a short-term (12 week treatment) clinical study to examine the role of ajulemic acid for patients with refractory dermatomyositis (DM) involving the skin. Patients with skin manifestations of dermatomyositis have extremely poor quality of life, including severe pruritus and depression, and current therapies are frequently ineffective. First line treatment for the skin is antimalarials, which frequently are not effective or cause drug reactions. We propose a randomized placebo-controlled clinical trial in DM patients with refractory skin disease, to test the safety and explore the clinical efficacy of ajulemic acid (AjA, a synthetic, nonpsychoactive, anti-inflammatory, analgesic cannabinoid, compared to placebo for the treatment of skin disease associated with DM. We anticipate that results from the proposed clinical trial will be used to power a larger Phase II clinical trial for clinical efficac of AjA. To test biological efficacy of AjA, serum levels and PBMC production of IL-1?, IFN?, IFN?, TNF?, and expression in PBMC of the IFN? signature will be examined before and after dosing. Successful completion of these studies should also allow us to determine biomarker endpoints for clinical efficacy to be used in a larger clinical trial. There is a great need for new approachs to treatment of the skin lesions of patients with dermatomyositis. This clinical study will allow careful observation of a potentially exciting new treatment.

Public Health Relevance

The overall goal of the proposed clinical study is to demonstrate the safety and anti- inflammatory properties of ajulemic acid (AjA), a synthetic, nonpsychoactive, anti- inflammatory, analgesic cannabinoid, in patients with skin-predominant forms of dermatomyositis (DM). The skin is one of the most visible and consistent findings in DM, seen in 85-95% of DM patients. There is a need for new effective and safer therapeutic approaches to treatment for patients with skin disease from DM that is refractory to antimalarials.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR066286-01
Application #
8691537
Study Section
(AMSC)
Program Officer
Witter, James
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Dermatology
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Fett, Nicole M; Fiorentino, David; Werth, Victoria P (2016) Practice and Educational Gaps in Lupus, Dermatomyositis, and Morphea. Dermatol Clin 34:243-50
Ang, C C; Anyanwu, C O; Robinson, E et al. (2016) Clinical signs associated with an increased risk of interstitial lung disease: a retrospective study of 101 patients with dermatomyositis. Br J Dermatol :
George, M D; Shah, R; Kreider, M et al. (2016) Pulmonary function tests, interstitial lung disease and lung function decline in outpatients with classic and clinically amyopathic dermatomyositis. Br J Dermatol :
Achtman, Jordan; Kling, Mitchel A; Feng, Rui et al. (2016) A cross-sectional study of untreated depression and anxiety in cutaneous lupus erythematosus and dermatomyositis. J Am Acad Dermatol 74:377-9
Schultz, Heather Y; Dutz, Jan P; Furukawa, Fukumi et al. (2015) From pathogenesis, epidemiology, and genetics to definitions, diagnosis, and treatments of cutaneous lupus erythematosus and dermatomyositis: a report from the 3rd International Conference on Cutaneous Lupus Erythematosus (ICCLE) 2013. J Invest Dermatol 135:7-12
Robinson, E S; Feng, R; Okawa, J et al. (2015) Improvement in the cutaneous disease activity of patients with dermatomyositis is associated with a better quality of life. Br J Dermatol 172:169-74
Anyanwu, C O; Fiorentino, D F; Chung, L et al. (2015) Validation of the Cutaneous Dermatomyositis Disease Area and Severity Index: characterizing disease severity and assessing responsiveness to clinical change. Br J Dermatol 173:969-74