Journal of Clinical and Aesthetic Dermatology

MauiDerm Abstract Supplement 2016

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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[ M AY 2 0 1 6 • V O L U M E 9 • N U M B E R 5 ] S U P P L E M E N T T O T H E J O U R N A L O F C L I N I C A L A N D A E S T H E T I C D E R M AT O L O G Y S15 e xcluded from psoriatic clinical trial assessments. This analysis compares the efficacy of a Class 3/4 betamethasone (DFD-01) and a Class 1 betamethasone (Diprolene, AugBD) o n knee and elbow plaques in subjects with moderate plaque psoriasis. Methods: Two Phase 3 clinical trials randomized adults with moderate psoriasis (Investigator Global A ssessment [IGA]=3; 10 to 20% BSA) to DFD-01, AugBD, or vehicle. Products were applied twice daily to all affected areas for 14 or 28 days. AugBD was applied for 14 days, per labelling. A target plaque, from either the elbow or knee of each subject was assessed. Success was assessed as (1) a score of 0 or 1 (reducing the plaque to "clear" or "slight to mild") for erythema, scaling, and plaque elevation; and (2) total sign score (TSS) ≤1 for all three signs (erythema, scaling, or plaque elevation) for a particular target lesion. Treatment success was analyzed post-hoc using Fisher's exact test. Results: Of the 628 subjects enrolled in these trials, 37.9 percent had a target lesion located on their elbow or knee selected for assessment (DFD-01, n=133; AugBD, n=32; Vehicle, n=71). Subanalysis of the pooled data shows that DFD-01 showed similar efficacy on hard-to- treat knee and elbow lesions as those treated with AugBD. In each measured outcome—erythema, scaling, plaque elevation, and TSS—results were superior with DFD-01 compared with AugBD at Day 4, although not significantly so. Day 15 success was seen in erythema (66.2% DFD-01 vs. 62.5% AugBD), scaling (70.7% DFD-01 v.s 62.5% AugBD), plaque elevation (65.4% DFD-01 vs. 62.5% AugBD), and TSS (53.4% DFD-01 vs. 43.8% AugBD). From Day 8, DFD-01 reduced erythema and scaling in significantly more subjects than vehicle (p≤0.003) and reduced plaque elevation in more subjects from Day 15 (p<0.001). DFD- 01 and AugBD also demonstrated comparative efficacy for lesions located on the trunk or extremities, with the exception of DFD-01 improving erythema in significantly more subjects than AugBD on Day 4 (p=0.024). C onclusion: DFD-01 effectively improved hard-to-treat lesions on knees and elbows. Improvements were seen in erythema, plaque elevation and, in particular, scaling. Responses w ere similar to those seen for lesions on the trunk and extremities. Financial disclosures/funding: Promius Pharma, Princeton, NJ A premilast for the Treatment of Psoriasis and Psoriatic Arthritis: Management of Gastrointestinal Adverse Effects Presenters: 1 Abraham BP; 2 Shah K; 2 Levi E; 3 Sellin JH Affiliations: 1 Houston Methodist – Weill Cornell, Houston, TX; 2 Celgene Corporation, Warren, NJ; 3 Baylor College of Medicine, Houston, TX Objective: Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, works intracellularly to regulate inflammatory mediators involved in the pathogenesis of psoriasis and psoriatic arthritis (PsA). Diarrhea and nausea are among the most common gastrointestinal adverse events (AEs) associated with PDE4 inhibitors. Here, we review the occurrence of diarrhea and nausea events thought to be drug related in the apremilast clinical trial program and provide practical clinical strategies for managing these events based on the literature on the management of drug-induced gastrointestinal symptoms and clinical experience. Methods: The safety and tolerability of oral apremilast 30mg twice daily have been evaluated in two Phase 3 clinical trials in patients with moderate- to-severe plaque psoriasis (ESTEEM 1 [NCT01194219] and ESTEEM 2 [NCT01232283]) and three Phase 3 clinical trials in patients with active PsA (PALACE 1 [NCT01172938], PALACE 2 [NCT01212757], and PALACE 3 [NCT01212770]); details of these studies have been published. No protocol definition for diarrhea or nausea was provided for these studies; frequency and specific stool characteristics (e.g., using the Bristol Stool Chart) were not assessed. Instead, diarrhea and nausea were documented from patients' reports and characterized as mild, moderate, or s evere according to patients and reporting investigators. Results: In the pooled clinical studies, most gastrointestinal AEs reported with oral apremilast 30mg t wice-daily treatment occurred early, were mild in severity, and resolved without intervention or dose modification. Patients treated with this dosing experienced diarrhea ( 16.5–17.8%) and/or nausea (15.1–16.6%) during the 0- to 16-week placebo-controlled periods. The majority of diarrhea or nausea events occurred within the first two weeks of treatment. Diarrhea and nausea were predominantly mild or moderate in nature. Most cases tended to resolve over time with continued dosing and without intervention; when treatment was used, loperamide was the most common agent used to manage gastrointestinal symptoms. Conclusion: Diarrhea and nausea are common AEs associated with apremilast treatment; they generally occur early, are mild in severity, and resolve without intervention. If needed, a number of non-pharmacologic and pharmacologic measures, based on the literature for drug-induced gastrointestinal symptoms, could be considered to manage gastrointestinal AEs in the short term with the goal of optimizing long-term treatment outcomes. We suggest counseling patients and setting expectations before treatment initiation to maximize treatment success. Non-pharmacologic measures should be considered first, including ensuring adequate hydration; taking medication with food (if not contraindicated); eating smaller, more frequent meals; and avoiding foods or drinks that exacerbate gastrointestinal symptoms. If symptoms persist, over- the-counter antidiarrheal or anti-nausea medications are options to consider; prescription agents for diarrhea or nausea are also available if needed. Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Moderate-to-Severe Plaque Psoriasis: Pooled 16-Week Efficacy in Patient Subgroups (ESTEEM 1 and 2) Presenters: 1 Neil J. Korman, MD; S 1 5

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