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Hidradenitis suppurativa (HS) is a frequently devastating inflammatory skin disorder. Although many treatments have been tried and tested to date, there is only one Food and Drug Administration-approved treatment option, adalimumab, which is currently indicated for moderateto- severe HS. Our understanding of the management of HS with biologic agents and with nonantibiotic and/ or antimicrobial systemic therapies continues to evolve. In this article, we summarize the existing data on biologics and other small-molecule systemic agents, as well as share our personal experiences with the pharmacological management of HS in the clinical setting. Continued challenges that limit our ability to study and treat this disease effectively include a lack of a universally employed scoring system for disease severity, high variability in clinical presentation, high cost of off-label therapy, and the scarcity of long-term studies on treatment response and medication safety., (©2018 Frontline Medical Communications.)

Background: Guselkumab, an interleukin-23 blocker, was superior to adalimumab in treating moderate to severe psoriasis in a phase II trial., Objectives: We sought to compare efficacy and safety of guselkumab with adalimumab and placebo in patients with psoriasis treated for 1 year., Methods: Patients were randomized to guselkumab 100 mg (weeks 0 and 4, then every 8 weeks; n = 329); placebo→guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20, then every 8 weeks; n = 174); or adalimumab (80 mg week 0, 40 mg week 1, then 40 mg every 2 weeks through week 47; n = 334). Physician-reported outcomes (Investigator Global Assessment, Psoriasis Area and Severity Index [PASI]), patient-reported outcomes (Dermatology Life Quality Index, Psoriasis Symptoms and Signs Diary), and safety were evaluated through week 48., Results: Guselkumab was superior (P < .001) to placebo at week 16 (85.1% vs 6.9% [Investigator Global Assessment score of 0/1 (cleared/minimal)] and 73.3% vs 2.9% [90% or greater improvement in PASI score from baseline (PASI 90)]). Guselkumab was also superior (P < .001) to adalimumab for Investigator Global Assessment 0/1 and PASI 90 at week 16 (85.1% vs 65.9% and 73.3% vs 49.7%), week 24 (84.2% vs 61.7% and 80.2% vs 53.0%), and week 48 (80.5% vs 55.4% and 76.3% vs 47.9%). Furthermore, guselkumab significantly improved patient-reported outcomes through week 48. Adverse event rates were comparable between treatments., Limitations: Analyses were limited to 48 weeks., Conclusions: Guselkumab demonstrated superior efficacy compared with adalimumab and was well tolerated in patients with psoriasis through 1 year., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Hidradenitis suppurativa is a painful, chronic inflammatory skin disease with few options for effective treatment. In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor α, showed efficacy against hidradenitis suppurativa., Methods: PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods. In period 1, patients were randomly assigned in a 1:1 ratio to 40 mg of adalimumab weekly or matching placebo for 12 weeks. In period 2, patients were reassigned to adalimumab at a weekly or every-other-week dose or to placebo for 24 weeks. The primary end point was a clinical response, defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts, at week 12., Results: We enrolled 307 patients in PIONEER I and 326 in PIONEER II. Clinical response rates at week 12 were significantly higher for the groups receiving adalimumab weekly than for the placebo groups: 41.8% versus 26.0% in PIONEER I (P=0.003) and 58.9% versus 27.6% in PIONEER II (P<0.001). Patients receiving adalimumab had significantly greater improvement than the placebo groups in rank-ordered secondary outcomes (lesions, pain, and the modified Sartorius score for disease severity) at week 12 in PIONEER II only. Serious adverse events in period 1 (excluding worsening of underlying disease) occurred in 1.3% of patients receiving adalimumab and 1.3% of those receiving placebo in PIONEER I and in 1.8% and 3.7% of patients, respectively, in PIONEER II. In period 2, the rates of serious adverse events were 4.6% or less in all the groups in both studies, with no significant between-group differences., Conclusions: Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups. (Funded by AbbVie; ClinicalTrials.gov numbers, NCT01468207 and NCT01468233 for PIONEER I and PIONEER II, respectively.).

Hidradenitis suppurativa is a severe and debilitating dermatologic disease. Clinical management is challenging and consists of both medical and surgical approaches, which must often be combined for best outcomes. Therapeutic approaches have evolved rapidly in the last decade and include the use of topical therapies, systemic antibiotics, hormonal therapies, and a wide range of immunomodulating medications. An evidence-based guideline is presented to support health care practitioners as they select optimal medical management strategies and is reviewed in this second part of the management guidelines. A therapeutic algorithm informed by the evidence available at the time of the review is provided.

Hidradenitis suppurativa is a chronic inflammatory disorder affecting hair follicles, with profoundly negative impact on patient quality of life. Evidence informing ideal evaluation and management of patients with hidradenitis suppurativa is still sparse in many areas, but it has grown substantially in the last decade. Part I of this evidence-based guideline is presented to support health care practitioners as they select optimal management strategies, including diagnostic testing, comorbidity screening, and both complementary and procedural treatment options. Recommendations and evidence grading based on the evidence available at the time of the review are provided.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can be challenging to treat. Biologics and targeted small molecules have become an increasingly popular area of investigation for therapeutic development for moderate-to-severe HS, though only three biologics—adalimumab, secukinumab, and bimekizumab—have received US Food and Drug Administration (FDA) or European Medicines Evaluation Agency approval for treating HS. Promising agents under investigation are targeting interleukin 17A/F, JAK/STAT pathway, interleukin 36, interleukin 1, and more. [ABSTRACT FROM AUTHOR]

Introduction: Hidradenitis suppurativa (HS) is a chronic, autoinflammatory skin disease associated with many comorbidities. One biologic (adalimumab) is approved for HS. This study assessed the sociodemographic characteristics, comorbidities, treatment patterns, healthcare resource utilization (HCRU) and associated costs of patients with HS following biologic approval. Methods: This non-interventional, retrospective cohort study involved adult (≥ 18 years) and adolescent (12–17 years) patients diagnosed with HS in the United States (US) using Optum's de-identified Clinformatics® Data Mart Database during the period 1 January 2016 to 31 December 2018. Results: Of 42,843 identified patients, 10,909 met the incident HS patient criteria (10,230 adults, 628 adolescents, 51 patients aged <12 years). Patients were mostly diagnosed by a general practitioner/pediatrician (adults: 41.6%; adolescents: 39.6%) or dermatologist (adults: 22.1%; adolescents: 30.6%). Commonly reported Charlson comorbidities at pre-index in adult patients were diabetes without complications (20.4%), chronic pulmonary disease (16.4%) and diabetes with complications (9.0%), and the most frequent Elixhauser comorbidities were uncomplicated hypertension (38.3%), obesity (22.5%), uncomplicated diabetes (19.0%) and depression (17.4%). The burden of comorbidities generally increased over time after diagnosis in both adults and adolescents. HS-related surgical procedures were uncommon in the 2-years post-index period: an incision and drainage procedure was reported in 7.6% of adults and 6.4% of adolescents. Patients were predominantly treated with both topical and systemic antibiotic treatments (adults: 25.0% and 65.1%, respectively; adolescents: 41.7% and 74.5%, respectively). Biologic prescription was higher in adults than adolescents (3.5% vs. 1.8%). Total healthcare costs for adult and adolescent patients in the 2-years post-index period were US$42,143 and US$16,057, respectively, with outpatient costs accounting for the majority of these costs (US$20,980 and US$8408, respectively). Conclusion: In adult and adolescent patients with HS, comorbidity burden continues to increase after diagnosis. All-cause and HS-specific HCRU and costs are high in adults and adolescents with HS. These findings support the need for a multidisciplinary comprehensive care strategy for patients with HS. [ABSTRACT FROM AUTHOR]

Background: Long-term maintenance treatment is required for patients with psoriasis.Objectives: To evaluate the efficacy and safety of guselkumab in patients with moderate to severe psoriasis through 3 years of treatment.Methods: In 2 ongoing, phase 3 trials of guselkumab (VOYAGE 1 and VOYAGE 2), the proportions of patients achieving at least 90% and 100% improvement in the Psoriasis Area and Severity Index (PASI 90 and PASI 100, respectively) and Investigator's Global Assessment (IGA) scores of 0/1 and 0 were summarized for the guselkumab group (including placebo-to-guselkumab crossover). Patients who met treatment failure rules were considered nonresponders. Safety outcomes (rates/100 patient-years [PY]) were evaluated based on data pooled across studies through week 156.Results: Three-year response rates for the guselkumab group in VOYAGE 1 and VOYAGE 2, respectively, were 82.8% and 77.2% for PASI 90, 50.8% and 48.8% for PASI 100, 82.1% and 83.0% for IGA score of 0/1, and 53.1% and 52.9% for IGA score of 0. Safety event rates across studies occurred through week 156 as follows: serious adverse events, 5.68/100 PY; serious infections, 1.15/100 PY; nonmelanoma skin cancers, 0.28/100 PY; malignancies other than nonmelanoma skin cancer, 0.47/100 PY; and major adverse cardiovascular events, 0.28/100 PY. Week 156 and week 100 rates were consistent.Limitations: There was no comparator arm beyond 1 year.Conclusions: Guselkumab shows durable efficacy and a consistent safety profile in patients with moderate to severe psoriasis treated for up to 3 years. [ABSTRACT FROM AUTHOR]

Patients with hidradenitis suppurativa (HS) are often undertreated and there are limited efficacious therapies available for treating this population. Biologics are an emerging therapeutic modality used in the management of many inflammatory conditions including HS. Implementation of biologics is typically reserved for moderate-to-severe cases or in those cases that are refractory to treatment. Though many biologics have been trialed for use in HS, only one biologic, adalimumab, is currently US FDA (Food and Drug Administration) approved for the treatment of moderate-to-severe HS. Limitations in the use of biologics for HS include the many scoring systems utilized in research studies and the relatively few well-designed, adequately powered clinical trials. [ABSTRACT FROM AUTHOR]

Background: Hidradenitis suppurativa (HS) is a chronic, painful skin disease characterized by abscesses, nodules, and draining fistulas in the axilla and groin of young adults. Objective: To evaluate the efficacy and safety of adalimumab, an anti-tumor necrosis factor-antibody, in patients with moderate to severe HS. Design: Phase 2, parallel, randomized, placebo-controlled trial consisting of a blinded 16-week period (period 1) and an open-label 36-week period (period 2). All study personnel, investigators, and patients remained blinded to treatment group throughout the study. Setting: 26 academic and private practice medical centers in the United States and Europe. Patients: 154 adult patients with moderate to severe HS who were unresponsive or intolerant to oral antibiotics. Intervention: Patients were assigned in a 1:1:1 ratio to adalimumab, 40 mg/wk; adalimumab, 40 mg every other week (EOW); or placebo. All patients received adalimumab, 40 mg EOW, at the beginning of period 2 but switched to weekly dosing if the response was suboptimal (HS Physician's Global Assessment [PGA] score of moderate or worse) at weeks 28 or 31. Measurements: The primary outcome measure (clinical response) was the proportion of patients achieving an HS-PGA score of clear, minimal, or mild with at least a 2-grade improvement relative to baseline at week 16. Results: At week 16, 3.9% of placebo patients (2 of 51), 9.6% of EOW patients (5 of 52), and 17.6% of weekly patients (9 of 51) achieved clinical response (EOW vs. placebo strata-adjusted difference, 5.6% [95% CI, -4.0% to 15.3%]; P = 0.25; weekly vs. placebo strata-adjusted difference, 13.7% [CI, 1.7% to 25.7%]; P = 0.025). Serious adverse event rates were 3.9%, 5.8%, and 7.8% for placebo, EOW, and weekly patients, respectively (EOW vs. placebo difference, 1.8% [CI, -6.4% to 10.1%]; weekly vs. placebo difference, 3.9% [CI, -5.2% to 13.0%]). Significantly greater improvements in patient-reported outcomes and pain were seen in the weekly dosing group than in the placebo group. A decrease in response was seen after the switch from weekly to EOW dosing in period 2. Limitations: Weeks 16 to 52 of the study were open-label. The study was not powered to assess the risk for known serious adverse effects of adalimumab, such as tuberculosis, other serious infections, and demyelinating disorders. Conclusion: Adalimumab dosed once per week alleviates moderate to severe HS. Primary Funding Source: Abbott Laboratories. [ABSTRACT FROM AUTHOR]

Objective: The effect of adalimumab on patient-reported outcomes (PROs) was evaluated in patients with moderate to severe psoriasis during the initial 16-week, double-blind period of a 52-week, Phase III, multicenter trial. Methods: Patients were randomized to placebo or adalimumab 80 mg at Week 0 and 40 mg every other week from Week 1 to Week 15. PROs were evaluated throughout the study and included the Dermatology Life Quality Index (DLQI), the Short Form 36 Health Survey (SF-36), the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (WPAI-SHP), and several patient-rated symptom scales. Results: The adalimumab-treated group reported significantly greater improvements in DLQI total score (p<0.001), SF-36 Physical Component Summary score (p<0.001), and Mental Component Summary score (p<0.001) compared with the placebo-treated group over 16 weeks. Significant differences, favoring adalimumab, were also seen for the DLQI subscale scores (p < 0.001); SF-36 scale scores (p<0.001); WPAI-SHP work impairment (p<0.001), activity limitation (p<0.001), and overall work impairment scores (p<0.001); patient's global assessment of disease severity (p<0.001), psoriasis pain (p<0.001), and psoriasis-related pruritus (p = 0.002). Conclusion: Adalimumab was efficacious in improving dermatology-specific and general health-related quality of life, work and activity limitations, and psoriasis-related symptoms in patients with moderate to severe psoriasis over a 16-week period. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Adalimumab for the treatment of moderate to severe hidradenitis suppurativa: a parallel randomized trial" in a 2012 issue along with a response from the authors of the article.

Background: Comparing effectiveness of biologics in real-world settings will help inform treatment decisions.Objectives: We sought to compare therapeutic responses among patients initiating infliximab, adalimumab, or etanercept versus ustekinumab during the Psoriasis Longitudinal Assessment and Registry (PSOLAR).Methods: Proportions of patients achieving a Physician Global Assessment score of clear (0)/minimal (1) and mean decrease in percentage of body surface area with psoriasis were evaluated at 6 and 12 months. Adjusted logistic regression (Physician Global Assessment score 0/1) and analysis of covariance (percentage of body surface area with psoriasis) were performed to determine treatment factors associated with effectiveness.Results: Of 2541 new users on registry, 2076 had efficacy data: ustekinumab (n = 1041), infliximab (n = 116), adalimumab (n = 662), and etanercept (n = 257). Patients receiving tumor necrosis factor-alpha(-α) inhibitors were significantly less likely to achieve Physician Global Assessment score 0/1 versus ustekinumab (infliximab [odds ratio {OR} 0.396, P < .0001], adalimumab [OR 0.686, P = .0012], etanercept [OR 0.554, P = .0003] at 6 months and infliximab [OR 0.449, P = .0040] at 12 months). Mean decrease in percentage of body surface area with psoriasis was significantly greater for ustekinumab versus adalimumab (point estimate 1.833, P = .0020) and etanercept (point estimate 3.419, P < .0001) at 6 months and versus infliximab (point estimate 3.945, P = .0005) and etanercept (point estimate 2.778, P = .0007) at 12 months.Limitations: Treatment selection bias and limited data for doing adjustments are limitations.Conclusions: In PSOLAR, effectiveness of ustekinumab was significantly better versus all 3 tumor necrosis factor-α inhibitors studied for the majority of comparisons at 6 and 12 months. [ABSTRACT FROM AUTHOR]