Brepocitinib, Zimlovisertib, and Ropsacitinib in Hidradenitis Suppurativa.

Kinase Inhibitors for Hidradenitis SuppurativaThree kinase inhibitor immunomodulators (daily oral brepocitinib, zimlovisertib, and ropsacitinib) were evaluated in this randomized, placebo-controlled trial of 194 patients with hidradenitis suppurativa. At 16 weeks, only brepocitinib, a JAK1/TYK2 inhibitor, achieved a higher clinical response than placebo (52% vs. 33%). The other two agents were no better than placebo.

Evaluating minority representation across health care settings in hidradenitis suppurativa and psoriasis.

Background: Females and minorities have been underrepresented in clinical research despite legislative efforts, including in hidradenitis suppurativa (HS) and psoriasis (PsO) clinical trials. Objective: To identify differences in demographic breakdowns of HS and PsO patients between health care settings to uncover any causative health disparities. Methods: This study reports racial, ethnic, and sex of HS and PsO patient populations across the emergency department (ED), inpatient, clinical trial, and registry settings. In addition, 95% confidence intervals are used as proxies of statistical significance to compare demographics between settings. Results: Female, Hispanic, and Black patients were underrepresented in HS clinical trials compared to their population prevalence (female: 63.7% vs 73.5%; Hispanic: 3.8% vs 12.0%; Black: 9.1% vs 20.3%). Female and Black patients were underrepresented in PsO trials compared to their population prevalence (female: 33.0% vs 54.8%; Black: 2.2% vs 5.7%). Black patients were overrepresented in the inpatient and ED settings in HS (inpatient vs ED vs population prevalence: 49.9% vs 49.9% vs 20.3%) and in the inpatient setting in PsO (inpatient vs population prevalence: 19.8% vs 5.7%). Limitations: The main limitation is the reliability and generalizability of the published studies used to compare demographics across settings. Conclusion: Underrepresentation of females and minorities in HS and PsO clinical trials is consistent with published literature. Overrepresentation of Black patients in acute care settings is likely multifactorial.

Efficacy and safety of the oral Janus kinase 1 inhibitor povorcitinib (INCB054707) in patients with hidradenitis suppurativa in a phase 2, randomized, double-blind, dose-ranging, placebo-controlled study.

BACKGROUND: Janus kinase 1 inhibition may alleviate hidradenitis suppurativa (HS)-associated inflammation and improve symptoms. OBJECTIVE: To assess efficacy and safety of povorcitinib (selective oral Janus kinase 1 inhibitor) in HS. METHODS: This placebo-controlled phase 2 study randomized patients with HS 1:1:1:1 to receive povorcitinib 15, 45, or 75 mg or placebo for 16 weeks. Primary and key secondary end points were mean change from baseline in abscess and inflammatory nodule count and percentage of patients achieving HS Clinical Response at week 16. RESULTS: Of 209 patients randomized (15 mg, n = 52; 45 mg, n = 52; 75 mg, n = 53; placebo, n = 52), 83.3% completed the 16-week treatment. At week 16, povorcitinib significantly reduced abscess and inflammatory nodule count from baseline (least squares mean [SE] change: 15 mg, -5.2 [0.9], P = .0277; 45 mg, -6.9 [0.9], P = .0006; 75 mg, -6.3 [0.9], P = .0021) versus placebo (-2.5 [0.9]). More povorcitinib-treated patients achieved HS Clinical Response at week 16 (15 mg, 48.1%, P = .0445; 45 mg, 44.2%, P = .0998; 75 mg, 45.3%, P = .0829) versus placebo (28.8%). A total of 60.0% and 65.4% of povorcitinib- and placebo-treated patients had adverse events. LIMITATIONS: Baseline lesion counts were mildly imbalanced between groups. CONCLUSION: Povorcitinib demonstrated efficacy in HS, with no evidence of increased incidence of adverse events among doses.

Secukinumab in the treatment of hidradenitis suppurativa.

The IL-17 pathways are involved in the pathophysiology of many inflammatory skin conditions, including hidradenitis suppurativa. Secukinumab, an IL-17A inhibitor, has been used for years in inflammatory skin disorders such as psoriasis. To date, the only US FDA-approved medication for hidradenitis suppurativa is adalimumab, a TNF-α inhibitor. Recently, secukinumab has demonstrated promising results in the treatment of hidradenitis suppurativa in the phase III SUNSHINE and SUNRISE clinical trials. This article reviews the mechanism of action of secukinumab and summarizes the available clinical efficacy and safety data regarding secukinumab in the management of hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic skin disorder characterized by recurrent painful bumps, tunnels underneath the skin and significant scarring. To date, the only US FDA-approved medication for hidradenitis suppurativa is adalimumab, a biologic medication that works on the immune system. Recently, a new biologic medication, secukinumab, has demonstrated promising results in the treatment of hidradenitis suppurativa in its phase III clinical trials. This article reviews how secukinumab works in the body, summarizes how well secukinumab has worked in treating hidradenitis suppurativa so far, and reviews common or serious side effects observed in patients with hidradenitis suppurativa as well as other chronic skin conditions.

Obstacles to Early Diagnosis and Treatment of Hidradenitis Suppurativa: Current Perspectives on Improving Clinical Management.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can progress to significant tunnels and scars that affect quality of life, especially if diagnosis and treatment are delayed. Average delay after initial presentation of HS symptoms can range from 3 to 10 years in adults and 1 to 2 years in children. Factors associated with diagnostic delay include female gender, non-white race, and greater disease severity at diagnosis. Contributing factors include misdiagnoses, difficulty accessing a dermatologist, hesitation in seeking care due to the stigmatizing nature of the disease, and lack of awareness among providers and patients. While efforts to increase awareness include academic talks at conferences and by foundations geared toward HS, social media offers the opportunity to reach young audiences. Many patients report dissatisfaction with their HS treatments. Better understanding of HS pathophysiology and implementation of clinically focused phenotypes and endotypes can lead to development of more targeted and efficacious therapies. FDA approval of medications for HS beyond adalimumab will increase access to a wider selection of therapies, and implementation of therapeutic drug monitoring may maximize the use of biologics for HS.

Impact of the COVID-19 Pandemic on the Delivery of Dermatological Care.

Purpose of Review: We review several important changes affecting dermatology during the COVID-19 pandemic, beginning in March 2020. Specifically, we focus on the impact of the COVID-19 pandemic on physician trends in employment, delivery of care via teledermatology, and burnout, resilience, and wellness. Recent Findings: More physicians are now employed by corporate entities than prior to the pandemic. Teledermatology can be utilized effectively and integrated into current care models; however, the continued use of teledermatology will largely depend on financial compensation. The COVID-19 pandemic was a source of burnout for all physicians, including dermatologists, and impacted how many people view their work. Summary: The COVID-19 pandemic pushed physicians to change their employment, required them to implement telehealth rapidly, and forced them to re-evaluate their priorities. Prior to the pandemic, more physicians transitioned into employed positions as compared to physician-owned practices. Multiple reasons for consolidation exist, but the trend accelerated during the COVID-19 pandemic for all medical specialties. Similarly, teledermatology was utilized prior to the pandemic, but its use exploded in the early days of the COVID-19 pandemic and continues to this day. The future of teledermatology though depends primarily on insurance reimbursement for these visits as well as both patient and physician preferences for continued usage. Lastly, wellness became a major focus in medicine as the pandemic took a significant toll on physicians, including dermatologists.

An Open-Label, Prospective, Pilot Study of Hypertonic Saline for Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) fistulas are likely to persist without surgical intervention. Hypertonic saline (HTS), a venous sclerosant, disrupts the endothelial lining leading to occlusion and fibrosis when used for venous insufficiency. OBJECTIVE: To evaluate the efficacy and tolerability of HTS sclerotherapy for HS fistulas. METHODS AND MATERIALS: This Institutional review board-approved, nonrandomized, clinical trial included adult patients with a diagnosis of HS and at least one confirmed HS fistula who underwent HTS injections into their fistulas every two weeks followed by a 4-week follow-up period. The study was performed from 2016 to 2019 at two academic outpatient dermatology clinics in Boston, MA. Primary outcomes were physician-assessed improvement of HS fistula characteristics between final and baseline visits and physician-assessed HS improvement during course of study. RESULTS: Overall, 21 patients participated. Physician-assessed overall HS improvement was significant between Visits 2 and 3 (p = .036). Drainage (p = .035), erythema (p = .008), and swelling (p = .025) demonstrated statistically significant improvement from baseline to final visit. Dermatology life quality index scores significantly improved from baseline to Visit 2 (p = .0005), Visit 3 (p = .0008), and final visit (p = .011). Numeric rating scale stinging scores increased with sclerosant volume. CONCLUSION: This study demonstrated physician-reported and patient-reported improvement in fistulas following serial HTS injections. HTS injections were well tolerated.

Advances in biologic and small molecule therapies for hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disorder characterized by painful nodules, abscesses, fistulae, and scarring with a predilection for flexural regions. Several biologics and small molecule inhibitors are being evaluated in clinical trials for treatment. AREAS COVERED: The authors discuss the data available from clinical trials and smaller, high-quality studies for existing and emerging biologic and small molecule inhibitor therapies for treatment of HS. Biologics discussed include TNFα, IL-17, IL-23, IL-12/23, and IL-1 inhibitors. Small molecule inhibitors discussed include PDE4, JAK, TYK, IFX-1, and complement cascade inhibitors. Pharmacokinetics and pharmacodynamics for these drugs are also described. EXPERT OPINION: Trial data and our own experience have shown that about half of HS patients experience improvement with adalimumab. However, there is a significant need for pharmacotherapies with higher efficacy goals as in those used for psoriasis. Many biologics and small molecule inhibitors are being tested in clinical trials. The landscape of upcoming therapies for hidradenitis suppurativa appears promising.

Yin and Yang of skin microbiota in "swimmer acne".

Cutibacterium acnes (C. acnes) is an organism implicated in the pathogenesis of acne. Despite regular immersion in antimicrobial chlorine, adolescent swimmers suffer from acne and tend to be resistant to standard therapies. Given the presence of Pseudomonas within swimming facilities, we hypothesized that "swimmer acne" is potentially driven by a different microbial mechanism. In this study, we aimed to examine the microbial dynamics of C. acnes and Pseudomonadaceae, a family of gram-negative bacteria (includes Pseudomonas aeruginosa), in swimmers and its potential contribution to the pathogenesis of acne in this population. Using fluorescence photography that measures the Coproporphyrin III (CPIII), we quantitated an absolute abundance of C. acnes present on the face of each participant pre- and post-swimming. In addition, 16S rRNA gene sequencing was utilized to assess relative abundance of the skin microbiota on each participant pre- and post-swimming. 16 swimmers (8 girls and 8 boys) completed the study. Seven had acne on the face. The CPIII fluorescence levels decreased for all swimmers after 1 h of swimming (p-value <0.001). In contrast, the relative abundance of C. acnes remained unchanged, while that of Pseudomonadaceae increased after swimming (p-value =0.027). Comparing the relative abundances of Pseudomonadaceae before swimming, there was a significant increase in variance from the mean in acne group as compared to no acne group (p-value <0.001). Taken together, we conclude that the skin dysbiosis resulting from repeated decolonization and colonization of C. acnes and Pseudomonadaceae, respectively, can potentially be associated with the pathogenesis of acne in swimmers.

Effects of swimming on facial sebum in adolescents.

Swimmers often complain of dry skin, consistent with decreased skin sebum levels, and yet may also have acne, which is commonly related to elevated sebum levels. Sixteen adolescent swimmers with and without acne were enrolled to examine two markers of facial sebum levels before and after 1 hour of swimming. Swimmers with acne did not have significant decreases in their sebum levels or shine measurements after swimming, whereas swimmers without acne did. Overall, swimming may remove superficial sebum more than follicular sebum and therefore leave swimmers subject to both dry skin and acne simultaneously.

Sunscreen recommendations for patients with skin of color in the popular press and in the dermatology clinic.

BACKGROUND: Patients with skin of color are at risk for skin cancer, pigmentary disorders, and photo-exacerbated conditions but find it challenging to use sunscreens on the market that leave an obvious residue on their skin. OBJECTIVE: The objective of this study was to examine sunscreen recommendations from the popular press and from practicing dermatologists for patients with skin of color. METHODS: We queried the Google search engine with the following search terms: "Sunscreen" with "skin of color," "dark skin," "black skin." For comparison, we also searched for "sunscreen" with "white skin," "pale skin," and "fair skin." We conducted an anonymous survey regarding sunscreen recommendations among dermatology trainees and board-certified dermatologists. RESULTS: Websites with recommendations on sunscreens for patients with skin of color compared with sunscreens for white or fair skin were more likely to recommend chemical sunscreens (70% vs. 36%) and more expensive products (median: $14 vs. $11.3 per ounce), despite the lower sun protection factor level (median: 32.5 vs. 50). In our survey study, dermatologists were overall cost-conscious and felt that sun protection factor level, broad spectrum (ultraviolet A/B protection), and price were the most important features of sunscreens for their patients. Cosmetic elegance was deemed least important. Dermatologists overall counseled patients with skin of color less on sunscreen use, and 42.9% reported that they either never, rarely, or only sometimes take patients' skin type into account when making sunscreen recommendations. CONCLUSION: These data represent an area for growth within dermatology to improve culturally competent care by gaining familiarity with sunscreen types and formulations that are geared toward patients with skin of color.

A safety review of biologic therapies for the management of hidradenitis suppurativa and unmet needs.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disorder characterized by nodules, abscesses, fistulae, and significant scarring in intertriginous areas rich in apocrine glands. Immunomodulator drugs, including biologics, are a mainstay of treatment for this disease. AREAS COVERED: This review details the safety profiles of various biologic therapies currently available commercially that have been tried for HS as assessed in clinical trials and observational studies. As the only Food and Drug Administration (FDA)-approved medication for the treatment of moderate-to-severe HS, adalimumab is discussed in the most detail. Additional biologic medications, including tumor necrosis factor α (TNFα) inhibitors, interleukin 1 (IL-1) inhibitors, IL-12 and IL-23 inhibitors, IL-17 inhibitors, and IL-23 inhibitors, are discussed as well. Safety concerns in special populations, including pregnant women and children, are outlined. EXPERT OPINION: Existing data support excellent short-term and long-term safety profiles for adalimumab, although caution must be taken with use in high-risk patient populations, including those with chronic infections or increased risk of malignancy. Based on their safety data for other indications, additional biologic agents appear safe in HS as well. However, further research is needed to fully understand the safety profiles of these medications in the HS population.