Data wobbles in hidradenitis suppurativa clinical trials and potential contributing factors: a retrospective review.

Background: In some hidradenitis suppurativa (HS) clinical trial study arms, there is an unexpected decline in efficacy between the penultimate visit and the prespecified primary endpoint week, which we have termed a "wobble." Objective: We aimed to establish how often study arms in HS programs wobble. Methods: In a retrospective review, we identified HS clinical trials listed on ClinicalTrials.gov testing systemic, nonantibiotic medications that utilized Hidradenitis Suppurativa Clinical Response (HiSCR) as an outcome measure. We identified study arms demonstrating greater improvement in a visit prior to the primary endpoint week. Baseline subject characteristics were compared between studies with HiSCR wobble and no HiSCR wobble. Results: A total of 21 studies (randomized control trial [RCT], n = 14; open-label, n = 7) with 35 study drug arms (RCT, n = 27; open-label, n = 8) and 14 placebo arms were identified. HiSCR wobble occurred significantly more often in RCT compared to open-label study drug arms (11/27 [40.7%] vs 0/8 [0%]). In RCT study arms with HiSCR wobble, baseline draining fistula counts were significantly lower (2.3 vs 3.2), and numerically fewer Hurley stage 3 patients (33.2% vs 42.5%), lower weighted total abscess and nodule counts (12.1 vs 12.6), lower weighted dermatology life quality index scores (12.5 vs 14.5), and a higher proportion of female patients (63.9% vs 58.3%) were observed. Limitations: Include low number of HS clinical trials and insufficient data reported in many studies to assess for wobble, degree of wobble, and to compare all baseline characteristics. Conclusion: Nonlinear improvement in study arm response occurs in some HS RCTs. Potential contributing factors include a higher proportion of less severe patients at baseline and more female patients.

Oral Psoriasis Therapies.

Oral psoriasis therapies include both older traditional immunosuppressants, such as methotrexate, cyclosporine, and acitretin, as well as newer, more targeted agents, such as apremilast, deucravacitinib, and oral interleukin-23 receptor antagonists. Patients may prefer oral therapies to injectable therapies based on the route of administration. Both older and newer oral psoriasis therapies can be utilized effectively in the treatment of psoriasis. Here, we will review oral agents used in the treatment of psoriasis as well as provide commentary on their role in our current, evolving psoriasis treatment paradigm.

Hematologic Abnormalities in Patients With Hidradenitis Suppurativa Receiving Adalimumab.

This post hoc analysis of PIONEER I and II randomized clinical trials assessed whether receiving adalimumab was associated with decreased hematologic abnormalities and increased clinical improvement in patients with hidradenitis suppurativa.

Brepocitinib, Zimlovisertib, and Ropsacitinib in Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating, inflammatory skin disease with limited treatment options and partially understood pathophysiology. Using an umbrella trial design, three kinase inhibitor immunomodulators with different mechanisms of action were evaluated. METHODS: This phase 2a, double-blind, parallel-group trial enrolled adults with moderate to severe HS who were then randomly assigned (1:1:1:1) to once-daily brepocitinib 45 mg (a JAK1/TYK2 inhibitor), zimlovisertib 400 mg (an IRAK4 inhibitor), ropsacitinib 400 mg (a TYK2 inhibitor), or matching placebo for 16 weeks. The primary end point was the percentage of participants achieving HS clinical response (HiSCR) at week 16. Safety, including treatment-emergent adverse events (TEAEs), was monitored throughout. RESULTS: Totals of 52, 47, 47, and 48 participants were assigned to brepocitinib, zimlovisertib, ropsacitinib, and placebo, respectively. At week 16, 28% were lost to follow-up and assumed to be nonresponders; HiSCR occurred in 33.3% (16/48) of participants receiving placebo and in 51.9% (27/52), 34.0% (16/47), and 37.0% (17/46) of those receiving brepocitinib, zimlovisertib, and ropsacitinib (difference in percentage points vs. placebo [90% confidence interval], 18.7 [2.7 to 34.6], 0.7 [−15.2 to 16.7], and 3.5 [−12.6 to 19.6]), respectively. TEAEs occurred more frequently with active treatment (brepocitinib, 30 [57.7%]; zimlovisertib, 26 [55.3%]; ropsacitinib, 29 [61.7%]; placebo, 23 [47.9%]). Most TEAEs (infections, skin disorders, and gastrointestinal symptoms) were mild; there were no deaths. CONCLUSIONS: Participants with moderate to severe HS treated with brepocitinib experienced greater clinical response, whereas those on zimlovisertib and ropsacitinib did not, compared with placebo. These results favor the JAK/STAT pathway as an immunologic target in HS and did not confirm a role for selective IRAK4 or TYK2 inhibition. These results should be confirmed in larger studies with longer follow-up. (Funded by Pfizer; ClinicalTrials.gov registration number, NCT04092452.)

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.

Infectious Disease Screening Prior to Systemic Immunomodulatory Therapy in Hidradenitis Suppurativa: Consensus Guidelines from the Asia-Pacific Hidradenitis Suppurativa Foundation.

BACKGROUND: Current infectious disease screening recommendations for hidradenitis suppurativa (HS) are adopted from recommendations in chronic plaque psoriasis. No HS-specific guidelines for infectious disease screening prior to immunomodulatory therapy have been developed. OBJECTIVES: To establish an expert Delphi consensus of recommendations regarding infectious disease screening prior to systemic immunomodulatory therapy in HS. METHODS: Participants were identified via recent publications in the field and were sent a questionnaire regarding infectious diseases encountered in the setting of HS, and opinions regarding infectious disease screening prior to various systemic immunomodulatory therapies. All questions were informed by a systematic literature review regarding infections exacerbated or precipitated by immunomodulatory therapy. Questionnaire responses were followed by round-table discussion with a core group of 8 experts followed by a final round of questionnaires resulting in achievement of consensus. RESULTS: 44 expert HS physicians from 12 countries on 5 continents participated in the development of the expert consensus recommendations. Consensus recommendations include screening for hepatitis B, hepatitis C and tuberculosis in all individuals with HS prior to therapy. All immunomodulatory therapies (biologic and systemic immunosuppressant therapy) should be preceded by infectious disease screening including patient and location specific considerations for endemic local diseases and high-risk activities and occupations. Clinical assessment has a significant role in determining the need for laboratory screening in the setting of many uncommon or tropical diseases such as leprosy, leishmaniasis and strongyloidiasis. CONCLUSIONS: The presented consensus recommendations are the first specifically developed for pre-treatment infectious disease screening in Hidradenitis Suppurativa.

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.

Implementing patient safety and quality improvement in dermatology. Part 1: Patient safety science.

Patient safety (PS) and quality improvement (QI) have gained momentum over the last decade and are becoming more integrated into medical training, physician reimbursement, maintenance of certification, and practice improvement initiatives. While PS and QI are often lumped together, they differ in that PS is focused on preventing adverse events while QI is focused on continuous improvements to improve outcomes. The pillars of health care as defined by the 1999 Institute of Medicine report "To Err is Human: Building a Safer Health System" are safety, timeliness, effectiveness, efficiency, equity, and patient-centered care. Implementing a safety culture is dependent on all levels of the health care system. Part 1 of this CME will provide dermatologists with an overview of how PS fits into our current health care system and will include a focus on basic QI/PS terminology, principles, and processes. This article also outlines systems for the reporting of medical errors and sentinel events and the steps involved in a root cause analysis.

Implementing patient safety and quality improvement in dermatology. Part 2: Quality improvement science.

Quality improvement (QI) in medicine is reliant on a team-based approach and an understanding of core QI principles. Part 2 of this continuing medical education series outlines the steps of performing a QI project, from identifying QI opportunities, to carrying out successive Plan-Do-Study-Act cycles, to hard-wiring improvements into the system. QI frameworks will be explored and readers will understand how to interpret basic QI data.

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.