Apremilast for the Treatment of Mild-to-Moderate Hidradenitis Suppurativa in a Prospective, Open-Label, Phase 2 Study
February 2019 | Volume 18 | Issue 2 | Original Article | 170 | Copyright © February 2019
Franz R. Kerdel DO, Fabio A. Azevedo CCRC, Christina Kerdel Don PA-C MCMSc, Frank A. Don DO, Gabriella Fabbrocini MD, Francisco A. Kerdel, BSc MBBS
Florida Academic Centers Research and Education Center, Miami, FL
BACKGROUND: Treatment options are limited for patients with hidradenitis suppurativa (HS). Apremilast, an oral phosphodiesterase 4 inhibitor, may offer an attractive therapeutic option for patients with mild-to-moderate HS.
METHODS: This open-label, phase 2 clinical trial enrolled adults (≥18 years of age) with mild-to-moderate HS. Patients received apremilast 30mg twice daily for 24 weeks after a 5-day titration period. Therapy was discontinued at week 24; data were collected up to week 28. Hidradenitis Suppurativa Clinical Response 30 (HiSCR30), ie, proportion of patients with a ≥30% reduction in abscesses and nodules at week 16, was the primary endpoint. HiSCR50, ie, ≥50% reduction, was also explored. Mean changes from baseline to week 24 in the modified Sartorius, Physician’s Global Assessment, visual analog scale (VAS) for pain, and Dermatology Life Quality Index (DLQI) scores were analyzed using the Wilcoxon Rank-Sum test. Adverse events (AEs) were summarized.
RESULTS: Twenty patients (mean age, 32.5 years) were enrolled in the study. HiSCR30 was achieved in 65% of patients at weeks 16 and 24. A similar proportion of patients achieved HiSCR50. Significant mean improvements from baseline were observed for all assessments. At week 24, the overall Sartorius score improved from 35.6 to 13.9 (-21.7 change; P less than 0.001), the PGA score from 2.7 to 1.6 (-1.1 change; P less than 0.01), the VAS pain score from 27.6 to 10.9 (-16.8 change; P less than 0.05), and the DLQI score from 11.6 to 5.4 (-6.2 change; P less than 0.01). Diarrhea (20%), nausea (15%), and depression (10%) were the most commonly reported AEs. No serious AEs or deaths were reported.
CONCLUSIONS: Apremilast was safe and effective in improving HS disease activity, pain, and QoL in patients with mild-to-moderate HS. These data suggest that apremilast may have a role in the early treatment of less severe HS.
J Drugs Dermatol. 2019;18(2):170-176.
Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease of the hair follicle1 that affects nearly 1% of the general population.1-3 This rare condition is most common in adults aged 20-29 years, after which the prevalence decreases with age.1,4 HS is also more common in women than men,1,4 and may have an increased prevalence in people with skin of color.5HS is typically characterized by painful, deep-seated, often malodorous lesions (including nodules, abscesses, and fistulas), and hypertrophic scars in areas with skin-to-skin contact and apocrine-rich areas, including the groin, armpits, underneath breasts, anus, buttocks, and inner thighs.6,7 Increased inflammation causes abscesses to rupture and release pus, and as abscesses heal, skin damage and permanent scarring often occur. These painful clinical manifestations can significantly impair the quality of life (QoL) of those affected,8,9 underscoring a substantial need for effective treatments.While surgery remains a common option to remove permanent sequelae caused by HS, and nonsurgical treatments seldom result in a lasting cure,10 a treatment that could prevent disease progression would be highly valuable. While no specific treatment algorithm has been established, European guidelines suggest patients be treated based on individual subjective impact and objective disease severity; with increasing severity, treatments typically begin with topical to systemic therapy, or increase in invasiveness for surgical options.10 Biologics are also suggested for more severe disease.10 The only FDA-approved biologic for patients with moderate-to-severe HS is adalimumab, a human, IgG1 monoclonal antibody that targets tumor necrosis factor α (TNF-α).11Apremilast is a highly specific, oral drug designed to inhibit the phosphodiesterase 4 enzyme, elevate intracellular cyclic adenosine monophosphate levels, and regulate pro- and anti-inflammatory mediators in inflammatory cells. The objective of this study was to evaluate the clinical safety and efficacy of apremilast for the treatment of mild-to-moderate HS. Patients with less severe disease were studied in an attempt to determine efficacy in early disease, since future strategies should prevent progression to more severe disease with irreversible sequelae.