Emerging drugs for the treatment of hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a severe, chronic inflammatory disorder that causes recurrent occlusion of hair follicles in the intertriginous regions of the skin. Mild to moderate HS has been successfully treated with oral antibiotics, topical therapy, and lifestyle modifications. However, moderate to severe HS is known to be refractory to conventional treatments. Wide excision surgery is a treatment option for severe HS, but often leads to functional impairments. Additionally, recurrence is common. The proper management of moderate to severe HS continues to be a challenge to practitioners. AREAS COVERED: A comprehensive literature search was conducted to identify published HS treatments using PubMed databases, in addition, ongoing studies were sought in clinicaltrials.gov. Search terms included 'hidradenitis suppurativa,' 'treatment,' and 'management.' EXPERT OPINION: Although adalimumab is currently the only biologic approved by the United States Food and Drug Administration for treatment of HS, there are many studies underway involving the development of drugs with a variety of immunological targets. Those potential HS therapies in either Phase II or Phase III trials show much promise. Since HS is a complicated disease that involves both pathological and environmental factors, treating HS continues to involve a multidisciplinary approach and monotherapy tends to not be efficacious.

Apremilast for the Treatment of Mild-to-Moderate Hidradenitis Suppurativa in a Prospective, Open-Label, Phase 2 Study

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<0.001), the PGA score from 2.7 to 1.6 (-1.1 change; P<0.01), the VAS pain score from 27.6 to 10.9 (-16.8 change; P<0.05), and the DLQI score from 11.6 to 5.4 (-6.2 change; P<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.

A phase 2, multicenter, double-blind, randomized, vehicle-controlled clinical study to compare the safety and efficacy of a halobetasol propionate 0.01% lotion and halobetasol propionate 0.05% cream in the treatment of plaque psoriasis.

Background: Halobetasol propionate (HP) 0.05% is a highly effective short-term treatment for plaque psoriasis. Objective: Compare efficacy and safety of once-daily HP 0.01% lotion and 0.05% cream (Ultravate®) in moderate-to-severe psoriasis. Methods: Multicenter, randomized, double-blind, vehicle-controlled Phase 2 study (N = 150). Patients randomized to HP 0.01% lotion, HP 0.05% cream, or vehicle, once-daily for 2 weeks. Efficacy assessments included treatment success; impact on erythema, plaque elevation, and scaling; and improvement in body surface area (BSA). Safety and treatment-emergent adverse events (TEAEs) were evaluated throughout. Results: 30.0% and 31.6% of patients were treatment successes with HP 0.01% lotion and HP 0.05% cream (p = .854). A 2-grade improvement in erythema, plaque elevation and scaling was achieved in 38.3%, 40.0%, and 43.3% of patients, compared with 31.6% (p = .446), 36.8% (p = .727), and 47.4% (p = .663) on HP 0.05% cream. BSA improved by 22.3% with HP 0.01% lotion compared with 20.9% (p = .787). There was one treatment-related application-site reaction with HP 0.01% lotion, and no AE reports of skin atrophy, striae, telangiectasia, or folliculitis. Conclusions: Halobetasol propionate 0.01% lotion was comparable to the higher concentration halobetasol propionate 0.05% cream; achieving treatment success, reducing psoriasis signs at the target lesion, and improving BSA following two weeks' daily-treatment. Both treatments were well-tolerated. Clinical Trials Registration: clinicaltrials.gov NCT02785185.

Safety and Efficacy of a Once-Daily Halobetasol Propionate 0.01% Lotion in the Treatment of Moderate-to-Severe Plaque Psoriasis: Results of Two Phase 3 Randomized Controlled Trials.

BACKGROUND: Topical corticosteroids (TCS) are the mainstay of psoriasis treatment; long-term safety concerns limiting consecutive use of potent TCS to 2-4 weeks. OBJECTIVE: Investigate safety and efficacy of halobetasol propionate 0.01% lotion in moderate-to-severe plaque psoriasis. METHODS: Two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies (N=430). Subjects randomized (2:1) to halobetasol propionate 0.01% lotion or vehicle once-daily for 8 weeks, 4-week posttreatment follow-up. Primary efficacy assessment: treatment success (at least a 2-grade improvement from baseline in Investigator Global Assessment [IGA] score and 'clear' or 'almost clear') at week 8. Safety and treatment emergent adverse events (AEs) evaluated throughout. RESULTS: Halobetasol propionate 0.01% lotion demonstrated statistically significant superiority over vehicle as early as week 2. By week 8, 36.5% (Study 1) and 38.4% (Study 2) of subjects were treatment successes compared with 8.1% and 12.0% on vehicle (P less than 0.001). Halobetasol propionate 0.01% lotion was also superior in reducing psoriasis signs and symptoms, body surface area (BSA), and improving quality of life. Halobetasol propionate 0.01% lotion was well-tolerated with no treatment-related AEs greater than 1%. LIMITATIONS: Study did not include subjects with BSA greater than 12. CONCLUSIONS: Halobetasol propionate 0.01% lotion was associated with significant reductions in the severity of the clinical signs of psoriasis, without the safety concerns of a longer treatment course. J Drugs Dermatol. 2018;17(10):1062-1069.

Update on TNF Inhibitors.

The introduction of tumor necrosis factor (TNF)-α inhibitors dramatically improved the management of psoriasis. Some newer or investigational biologics with different mechanisms of action have demonstrated noninferiority or superiority to etanercept, the first self-injectable anti-TNF-α agent to become available in the United States. Nonetheless, TNF-α inhibitors are likely to remain a mainstay of therapy for many years.

The risk of malignancy or progression of existing malignancy in patients with psoriasis treated with biologics: case report and review of the literature.

There is some debate regarding the risk of developing malignancy and progression of malignancy in patients with psoriasis treated with biologics. The lack of extensive, long-term, and large studies, including patients with psoriasis, to assess these aforementioned risks makes it difficult to ascertain the safety profile of biologic therapy in these patients. Several studies do support the favorability of the safety profile of biologics in patients with psoriasis in terms of the risk of developing malignancy. A few studies include patients with a previous history of cancer that were thereafter treated with biologics and show no increased risk of recurrence in those treated with biologics compared to non-biologic therapy. Although recent studies do not show an increased risk of new or recurrent malignancy in patients with psoriasis treated with biologic agents, there is still hesitancy in the widespread use of biologic agents in these patients. Considering all of the current data and opinions, the benefits of biologic therapy to improve quality of life often outweigh the negligible risk of solid organ malignancy associated with biologics in patients with existing or previous malignancies. Coordinating the management of patients that develop or have a history of previous malignancy with an oncology team is crucial for patient-centered care until clear evidence-based guidelines are developed.

TNF Inhibitors in Psoriasis: A Review.

Adalimumab, etanercept, and infliximab are tumor necrosis factor (TNF) inhibitors that are currently approved by the US Food and Drug Administration for the treatment of moderate to severe psoriasis. The availability of these biologic agents established a new benchmark in the treatment of psoriasis that requires systemic therapy to control psoriasis signs and symptoms. Although a number of other biologic agents and small molecules have been approved recently, TNF inhibitors remain a cornerstone of psoriasis therapy. Semin Cutan Med Surg 34(supp2):S37-S39 © 2015 published by Frontline Medical Communications.

Dermabrasion: a novel treatment for diffuse silicone granuloma.

OBJECTIVE: Formation of a foreign body granuloma is one of the serious complications of silicone injection, which can be difficult to treat. In this paper, the authors report their successful experience with dermabrasion as an innovative treatment in a patient who presented with diffuse silicone granuloma. CASE REPORT: The patient was a 51-year-old woman, with areas of induration and hyperpigmentation on both her legs with intermittent fevers and generalized malaise. The patient had a history of numerous bilateral hip injections of liquid silicone five years ago for cosmetic purposes. A skin biopsy showed a foreign-body granuloma consistent with a paraffinoma with "Swiss cheese" appearance. After unsuccessful medical therapy and liposuction, an extensive bilateral dermabrasion was performed on both legs. Postoperatively, her wounds exuded a collection of thick, yellow viscous fluid under the transparent semi-occlusive dressings, which showed a markedly elevated level of silicone after analysis. She experienced no complication related to dermabrasion. CONCLUSION: The findings of this case demonstrate that dermabrasion may be an effective treatment option for diffuse silicone granuloma, particularly when the material resides superficially in the dermis.

Optimizing the use of topical brimonidine in rosacea management: panel recommendations.

Rosacea is a chronic inflammatory disease with a complex pathophysiology that manifests with central facial redness with or without papulopustular lesions. Often, patients with rosacea present with a constellation of signs and symptoms; for best results, the treatment plan should take into account all symptoms manifesting in the individual patient. The first available pharmacologic treatment to address the redness associated with rosacea is topical brimonidine. In the United States, brimonidine topical gel 0.33% is indicated for persistent facial erythema of rosacea; approval was based on clinically significant efficacy and good safety data from large-scale clinical trials. Use of brimonidine in routine clinical practice has yielded new insights that elaborate on the findings from clinical trials. For example, real-world use has shown that a percentage of patients (in our experience, approximately 10 to 20%) treated with brimonidine experience a worsening of erythema that has been called "rebound." Our routine use of this agent for >1 year has yielded strategies to set patient expectations, optimize treatment initiation, and minimize potential problems; this article details those strategies. Because we believe that the term "rebound" has been used to describe several physiologically distinct events, we have also proposed more specific terminology for such events.

Current and emerging nonsurgical treatment options for hidradenitis suppurativa.

Several nonsurgical strategies for managing hidradenitis suppurativa (HS) are used that are successful in many patients. The overall goals of pharmacologic therapy are to clear or reduce the number and extent of current lesions and to prevent new lesions from forming. No pharmacologic agent is universally effective in all patients with HS, and, to date, none has been approved for this indication by the US Food and Drug Administration. Among the agents most commonly used are topical and systemic antibiotics and intralesional and systemic corticosteroids. Within the past decade, clinical experience with biologic agents-principally, tumor necrosis factor inhibitors-has been described, and the results of clinical trials with these agents in patients with HS have been promising.

Tumor necrosis factor inhibitors in psoriasis: an update.

Three inhibitors of tumor necrosis factor (TNF) currently are approved for the treatment of psoriasis: etanercept, infliximab, and adalimumab. The other two TNF inhibitors, golimumab and certolizumab pegol, have shown efficacy against plaque psoriasis in clinical trials of psoriatic arthritis (PsA). This article reviews the most recent evidence on the efficacy and safety of the TNF inhibitors in psoriasis, with special attention to preventing and managing immunogenicity.