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.

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.

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.

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.

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.

Cutaneous metastasis of cervical adenocarcinoma to the vulva.

Cervical cancer is one of the most common cancers and cause of cancer-related deaths in women worldwide. Cutaneous metastasis of cervical cancer, however, is exceedingly rare. It is generally seen late in the disease course and portends a poor prognosis. Herein we report a woman with a history of recurrent cervical cancer complicated by an unusual occurrence of metastasis to the vulva.

Erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis associated with lupus erythematosus.

BACKGROUND: The occurrence of erythema multiforme (EM)-like lesions in association with lupus erythematosus (LE) is often referred to as "Rowell syndrome" (RS). However, the existence of RS, or at least its nosographic independence from LE, is questioned. The association of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with LE is also controversial. OBJECTIVE: We sought to define the features of EM and SJS/TEN in the setting of LE. METHODS: The worldwide literature on the topic was systematically collected and reviewed. RESULTS: A total of 132 citations were found, from which 95 cases of EM-like lesions and 47 of SJS/TEN associated with LE were retrieved. Our analysis identified a subgroup defined as "subacute cutaneous LE (CLE)/acute CLE with EM-like lesions" and highlighted that this and subacute CLE/acute CLE with TEN-like lesions are variants of already known CLE subpatterns. On the other hand, RS can be considered an independent chronic CLE subtype characterized by the distinctive co-occurrence of chronic CLE and EM-like lesions and frequent, albeit mild, systemic involvement. LIMITATIONS: The study was based on retrospective data and the number of reported cases identified was relatively small. CONCLUSION: RS might be included as a chronic CLE subtype within the spectrum of LE-specific skin disease.

The efficacy and safety of infliximab in patients with plaque psoriasis who had an inadequate response to etanercept: results of a prospective, multicenter, open-label study.

BACKGROUND: In patients with psoriasis and inadequate response (IR) to tumor necrosis factor-α antagonist treatment, the incremental benefit of switching to another tumor necrosis factor-α antagonist is unknown. OBJECTIVE: We sought to evaluate the clinical response to an etanercept-to-infliximab switch in patients with psoriasis and IR to etanercept. METHODS: Adults with moderate-to-severe plaque psoriasis and IR to etanercept (≥ 4 months) were eligible for this open-label study (called PSUNRISE). Patients had a Physician Global Assessment (PGA) score of at least 2 (mild) on a 5-point scale with etanercept, with or without concomitant oral systemic methotrexate or cyclosporine at baseline and during the study. Patients received intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, 14, and 22. PGA was used to evaluate efficacy at week 10 (primary end point) and week 26 (durability). Safety was evaluated through the end of the study. RESULTS: Of 215 patients, only 10 received concomitant immunomodulators. At week 10, 65.4% of patients (138 of 211; 95% confidence interval 58.6%-71.8%) achieved a PGA score of clear (0) or minimal (1) (primary end point). This response was durable through week 26, at which time 61.3% (122 of 199; 95% confidence interval 54.2%-68.1%) achieved a PGA score of clear (0) or minimal (1). There were no unexpected side effects or safety concerns. LIMITATIONS: This was an open-label, 26-week study; an incremental change of 1 PGA point, even mild to minimal, was considered clinically significant, as most psoriasis practitioners seek to achieve minimal psoriasis or clear skin. CONCLUSION: After switching to infliximab, a substantial proportion of patients with psoriasis and IR to etanercept experienced rapid and durable improvement.

The use of cyclosporine in dermatology.

Cyclosporine is an immunosuppressive drug that acts selectively on T-cells by inhibiting calcineurin phosphorylase. It has been used in dermatology since its approval for US Food and Drug Administration in 1997 for the use in psoriasis. While indicated only for the treatment of moderate to severe psoriasis, cyclosporine has also been used as an off-label drug for the treatment of various inflammatory skin conditions, including atopic dermatitis, blistering disorders, and connective tissue diseases. In this article, we review the use of cyclosporine in dermatology.

Switching to adalimumab for psoriasis patients with a suboptimal response to etanercept, methotrexate, or phototherapy: efficacy and safety results from an open-label study.

BACKGROUND: Strategies for transitioning patients with psoriasis from suboptimal therapy have not been delineated. OBJECTIVE: We sought to determine the efficacy and safety of transitioning to adalimumab for the treatment of psoriasis in patients with suboptimal response to prior therapy with etanercept, methotrexate (MTX), or narrowband (NB)-ultraviolet (UV)B phototherapy. METHODS: In this 16-week, open-label, phase IIIb trial, patients with chronic plaque psoriasis discontinued suboptimal therapy between 11 and 17 days (etanercept) or between 4 and 10 days (MTX and NB-UVB) before initiating adalimumab (80 mg at week 0, then 40 mg every other week from week 1). The primary end point was the percentage of patients achieving a Physician Global Assessment of "clear" or "minimal" at week 16. RESULTS: At week 16, Physician Global Assessment of "clear" or "minimal" was achieved by 52% of all enrolled patients (79 of 152) and 49%, 61%, and 48% in the etanercept, MTX, and NB-UVB subgroups, respectively. Four patients (2.6%) experienced at least 125% worsening of Psoriasis Area and Severity Index score relative to screening value at any study visit. The adalimumab safety profile was consistent with results from other psoriasis clinical trials. LIMITATIONS: This study is limited by its relatively short 16-week duration, small patient enrollment, and open-label design. CONCLUSION: Patients who had a suboptimal response to etanercept, MTX, or NB-UVB phototherapy experienced a similar, approximately 50% likelihood of achieving a clinically relevant response to adalimumab. Immediate transition to adalimumab from prior suboptimal therapy, with no dosage tapering or overlap, had a low risk of psoriasis flare.

Fatal cutaneous Strongyloidiasis as a side effect of Pemphigus foliaceus treatment with mycophenolate mofetil.

Strongyloidiasis is caused by the roundworm Strongyloides stercoralis (S. stercoralis). It is uncommon in the Unites States, and most cases are brought by travelers who have visited or lived in South America or Africa. Individuals with an intact immune system may experience mild gastrointestinal symptoms or none at all. In contrast, those with a compromised immune system may develop a rapidly fatal infection, commonly referred to as hyperinfection syndrome or disseminated Strongyloidiasis. We present a 66-year-old inmunocompromised male with Pemphigus Foliaceus who was admitted to the intensive care unit in critical condition and in whom a skin biopsy prove to be the main tool in the diagnosis of Strongyloidiasis.

Infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo-controlled crossover trial.

BACKGROUND: Biologic therapies with anti-tumor necrosis factor agents are promising treatments for hidradenitis suppurativa (HS). OBJECTIVE: We assessed the efficacy and safety of infliximab (IFX) for the treatment of moderate to severe HS. METHODS: A prospective double-blind treatment phase of 8 weeks where patients received IFX or placebo was followed by an open-label phase where patients taking placebo were given the opportunity to cross over to IFX, and an observational phase. Primary treatment efficacy was based on HS Severity Index. Secondary end points included Dermatology Life Quality Index, visual analog scale, and Physician Global Assessment scores. Inflammatory markers erythrocyte sedimentation rate and C-reactive protein were also assessed. RESULTS: More patients in the IFX than in the placebo group showed a 50% or greater decrease from baseline HS Severity Index score. In addition, statistically and clinically significant improvement from baseline was observed at week 8 in Dermatology Life Quality Index score, visual analog scale score, erythrocyte sedimentation rate, and C-reactive protein compared with placebo. Patients in the placebo group treated with IFX after week 8 (crossover) responded similarly to the original IFX group. Many patients withdrew during the observational phase to continue anti-tumor necrosis factor-alfa therapy. No unexpected serious adverse events were observed. LIMITATIONS: Results are representative of a single center, patients were treated by a single physician, some patients did not return after their last infusion, and the HS Severity Index requires validation. CONCLUSIONS: This clinical study represents the first formal assessment of IFX for treatment of moderate to severe HS. IFX was well tolerated, no unexpected safety issues were identified, and improvements in pain intensity, disease severity, and quality of life were demonstrated with concomitant reduction in clinical markers of inflammation.