Evaluating Safety & Efficacy of Apremilast in the Treatment of Cutaneous Disease in Patients With Recalcitrant Dermatomyositis

Summary

With limited treatment options available for dermatomyositis, the investigators hypothesize that apremilast, a phosphodiesterase-4 (PDE-4) inhibitor, is a safe and efficacious add-on treatment in patients with refractory cutaneous dermatomyositis. The study will investigate the efficacy, safety and toxicity of apremilast given at 30 mg twice daily to patients with refractory cutaneous dermatomyositis. Clinical response will be assessed at 1 and 3 months. Patients will also be evaluated for durability of their response for up to 6 months. Treatment will be monitored with frequent clinical visits (0, 1, 3 and 6 months) and blood tests (CBC, CMP, creatine kinase, aldolase). Treatment will be discontinued at disease progression or unacceptable adverse events. Disease progression is defined as 4 points increase in the cutaneous dermatomyositis disease area and severity index (CDASI) score, worsening of muscle disease by manual muscle testing (MMT-8) score and 5 points increase in dermatomyositis life quality index (DLQI). 5 mm skin biopsies from lesional skin will be performed before treatment with apremilast and after 3 months of treatment for gene expression profiling and confirmatory immunohistochemical stains.

Timeline

Start

2018-06-12

Primary completion

2021-02-28

Completion

2021-04-07

Publications

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• Background Giris M, Durmus H, Yetimler B, Tasli H, Parman Y, Tuzun E. Elevated IL-4 and IFN-gamma Levels in Muscle Tissue of Patients with Dermatomyositis. In Vivo. 2017 Jul-Aug;31(4):657-660. doi: 10.21873/invivo.11108.
• Background Oda K, Kotani T, Takeuchi T, Ishida T, Shoda T, Isoda K, Yoshida S, Nishimura Y, Makino S. Chemokine profiles of interstitial pneumonia in patients with dermatomyositis: a case control study. Sci Rep. 2017 May 9;7(1):1635. doi: 10.1038/s41598-017-01685-5.
• Background Maier C, Ramming A, Bergmann C, Weinkam R, Kittan N, Schett G, Distler JHW, Beyer C. Inhibition of phosphodiesterase 4 (PDE4) reduces dermal fibrosis by interfering with the release of interleukin-6 from M2 macrophages. Ann Rheum Dis. 2017 Jun;76(6):1133-1141. doi: 10.1136/annrheumdis-2016-210189. Epub 2017 Feb 16.
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• Background Saba NS, Liu D, Herman SE, Underbayev C, Tian X, Behrend D, Weniger MA, Skarzynski M, Gyamfi J, Fontan L, Melnick A, Grant C, Roschewski M, Navarro A, Bea S, Pittaluga S, Dunleavy K, Wilson WH, Wiestner A. Pathogenic role of B-cell receptor signaling and canonical NF-kappaB activation in mantle cell lymphoma. Blood. 2016 Jul 7;128(1):82-92. doi: 10.1182/blood-2015-11-681460. Epub 2016 Apr 28.
• Background Saba NS, Wong DH, Tanios G, Iyer JR, Lobelle-Rich P, Dadashian EL, Liu D, Fontan L, Flemington EK, Nichols CM, Underbayev C, Safah H, Melnick A, Wiestner A, Herman SEM. MALT1 Inhibition Is Efficacious in Both Naive and Ibrutinib-Resistant Chronic Lymphocytic Leukemia. Cancer Res. 2017 Dec 15;77(24):7038-7048. doi: 10.1158/0008-5472.CAN-17-2485. Epub 2017 Oct 9.
• Background Akbulut S, Yilmaz M, Yilmaz S. Graft-versus-host disease after liver transplantation: a comprehensive literature review. World J Gastroenterol. 2012 Oct 7;18(37):5240-8. doi: 10.3748/wjg.v18.i37.5240.
• Background Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994 May;19(3):210-6. doi: 10.1111/j.1365-2230.1994.tb01167.x.
• Background Rider LG, Werth VP, Huber AM, Alexanderson H, Rao AP, Ruperto N, Herbelin L, Barohn R, Isenberg D, Miller FW. Measures of adult and juvenile dermatomyositis, polymyositis, and inclusion body myositis: Physician and Patient/Parent Global Activity, Manual Muscle Testing (MMT), Health Assessment Questionnaire (HAQ)/Childhood Health Assessment Questionnaire (C-HAQ), Childhood Myositis Assessment Scale (CMAS), Myositis Disease Activity Assessment Tool (MDAAT), Disease Activity Score (DAS), Short Form 36 (SF-36), Child Health Questionnaire (CHQ), physician global damage, Myositis Damage Index (MDI), Quantitative Muscle Testing (QMT), Myositis Functional Index-2 (FI-2), Myositis Activities Profile (MAP), Inclusion Body Myositis Functional Rating Scale (IBMFRS), Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), Cutaneous Assessment Tool (CAT), Dermatomyositis Skin Severity Index (DSSI), Skindex, and Dermatology Life Quality Index (DLQI). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11(0 11):S118-57. doi: 10.1002/acr.20532. No abstract available.
• Bitar C, Ninh T, Brag K, Foutouhi S, Radosta S, Meyers J, Baddoo M, Liu D, Stumpf B, Harms PW, Saba NS, Boh E. Apremilast in Recalcitrant Cutaneous Dermatomyositis: A Nonrandomized Controlled Trial. JAMA Dermatol. 2022 Dec 1;158(12):1357-1366. doi: 10.1001/jamadermatol.2022.3917.

Drugs

Indications