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.

New insights on hidradenitis suppurativa phenotypes and treatment response: An exploratory automated analysis of the SUNSHINE and SUNRISE trials.

BACKGROUND: Defining hidradenitis suppurativa (HS) subtypes was previously limited by small sample sizes and poor interrater reliability; no study has investigated subtype treatment responses. The objective of this analysis was to characterize HS clusters in adult patients with moderate to severe HS and evaluate secukinumab treatment responses between clusters. METHODS: Clusters were identified via an unsupervised machine learning clustering analysis using baseline data from the randomized, placebo-controlled SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) phase 3 trials. To assess treatment responses, patients received secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W) or placebo, for 16 weeks, after which, placebo patients randomly switched to SECQ2W/SECQ4W, and SECQ2W/SECQ4W patients maintained their original treatment, until week 52. Baseline outcomes included patient characteristics, disease characteristics and severity, HS-associated comorbidities and previous treatment exposures. Treatment response was assessed via the HS clinical response (HiSCR), abscess and inflammatory nodule (AN) count, flares and NRS30 (skin pain). RESULTS: Based on baseline data, three clusters were identified from 1084 patients (Cluster 1: 54.1%, Cluster 2: 17.8%, Cluster 3: 28.1%). Cluster 1 was predominantly female (65.4%) and was characterized by milder HS. Cluster 2 had more patients from the Asia Pacific, Middle East and Africa region (58.5%) and was characterized by moderate HS. Cluster 3 had the highest rates of previous exposure to biologics (45.9%) and prior HS-related surgeries (47.5%) and was characterized by severe HS. SECQ2W and SECQ4W demonstrated efficacy versus placebo in all clusters at week 16; SECQ2W and SECQ4W efficacy was maintained to week 52. SECQ2W treatment showed a trend for greater efficacy versus SECQ4W in Cluster 3 through week 52. CONCLUSIONS: Three HS clusters were identified. Secukinumab demonstrated benefit over placebo in all clusters. However, patients with more severe disease may take longer to respond and more frequent secukinumab dosing may be required for these patients. TRIAL REGISTRATION: SUNSHINE (NCT03713619) and SUNRISE (NCT03713632).

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.

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.

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.

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.

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.

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.

Physician perspectives on complementary and alternative medicine in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic and often debilitating inflammatory condition characterized by frequent nodules, abscesses, sinus tracts, and scars impacting the intertriginous areas. Many patients with HS often report limited treatment success and symptom coverage with conventional therapies. Recent studies have reported the widespread use of complementary and alternative medicine (CAM) among patients with HS. In this study, our aim was to examine current physician practice patterns, opinions, and comfort with recommending CAM. Our results indicate that provider comfort and opinions on CAM varied based on the provider's experiences, demographics, and the CAM modality itself. Overall, nearly two-thirds (n = 30, 61.2%) of respondents agreed that CAM and conventional medicine were more effective together than either alone. Meanwhile, 44.9% (n = 22) of respondents routinely recommend CAM while 64.6% (n = 31) of respondents reported that they are routinely asked about CAM. The majority (n = 41, 83.7%) of respondents indicated a lack of scientific evidence in the medical literature as a barrier to recommending CAM along with efficacy concerns (n = 34, 69.4%) and ability to recommend reputable CAM products (n = 32, 65.3%) and practitioners (n = 32, 65.3%). Future investigations are warranted to establish a better understanding of the efficacy and benefit of CAM methods in conjunction with conventional methods.

Antiandrogen therapy with spironolactone for the treatment of hidradenitis suppurativa.

BACKGROUND: Hormonal therapy is a potential treatment for hidradenitis suppurativa (HS). However, few data exist describing the efficacy of spironolactone in treatment of HS. OBJECTIVE: To assess whether spironolactone treatment improves HS disease severity and patient-reported pain. METHODS: We performed a single-center chart review of female patients with HS who were treated with spironolactone between 2000 and 2017. Primary outcome measurements included the HS Physician's Global Assessment (HS-PGA), Hurley staging, inflammatory lesion count, fistula count, and a numeric rating scale for pain. RESULTS: On average, subjects were exposed to 75 mg of spironolactone daily over a 7.1-month follow-up period. Patients achieved significant disease improvement with regard to pain (Δ-1.5 [P = .01]), inflammatory lesions (Δ-1.3 [P = .02]), and HS-PGA score (Δ-0.6 [P < .001]). As expected, no change was found for Hurley stage (Δ0 [P = .32]) or fistulas (Δ0 [P = .73]). There was no difference in improvement between subjects who received less than 75 mg of spironolactone daily (n = 25; average dose, 45 mg/d) and those who received more than 100 mg daily (n = 21; average dose, 112 mg/d). LIMITATIONS: Retrospective nature, limited sample size, and variations in severity measures documented were limiting factors. CONCLUSIONS: Management of HS with spironolactone reduces lesion count, HS-PGA score, and pain. Lower doses appear to be effective and may be an appropriate option for patients with tolerability concerns.

Examining the prior authorization process, patient outcomes, and the impact of a pharmacy intervention: A single-center review.

BACKGROUND: Dermatology experiences a disproportionately high burden of prior authorizations (PAs). OBJECTIVE: To examine the effect of a centralized pharmacy intervention on the PA process and the impact of PAs on patient outcomes. METHODS: A retrospective review of PAs submitted for medications before and after implementation of pharmacy intervention was conducted. RESULTS: PA was required for 8.1% of all prescriptions. PAs were most frequently submitted for topical steroids, topical antibiotics and antifungals, and topical retinoids. Most common indications included acne, psoriasis, and dermatitis. Biologic agents (55.2%) and brand-name only medications (42.8%) required PA at higher rates. Pharmacy intervention resulted in shorter time to PA submission (4 days vs 1 day, P < .001) and decision (6 days vs 1 day, P < .001) and higher approval rates (63.9% vs 80.6%, P < .001) but did not decrease the total number of PAs. Patients with approved PAs had higher likelihood of disease improvement vs those with denied PAs (71.1% vs 58.0%, P = .013). LIMITATIONS: Data were collected from a single academic institution. Patient medication compliance was not assessed. CONCLUSIONS: The current PA process may result in delays in care and a negative impact on patients. A centralized pharmacy intervention is an effective measure but does not eliminate the overall burden of PAs.

Discordance Between Patient Reported Motivations to Seek Treatment for Psoriasis Compared to Television Advertisements.

INTRODUCTION: Despite a growing arsenal of therapies for psoriasis and, consequently, an increasing number of advertisements for these treatments, many psoriasis patients still remain untreated. While the primary treatment seeking motivations for these patients have been identified, it is unknown if the commercials for the medications designed to encourage patient engagement in treatment are relevant to these concerns. METHODS: Online databases for national television advertisements were searched for psoriasis treatment commercials broadcast between 2000 and 2018. Each advertisement video was viewed 3 times and separately assessed for the content displayed or information conveyed in images, text, and voice-over speech. Additionally, references to known patient motivations for seeking treatment, including concerns about skin symptoms or appearance (embarrassment, scaling/flaking, pain, discomfort, itch, etc.) were recorded. RESULTS: A total of 20 commercials were assessed. Of those, 100% emphasized "clear skin" as the result of the treatment that was being marketed. Bothersome skin symptoms, however, were less frequently displayed; scaling/flaking, pain/discomfort, and itch were present in 15%, 5%, and 0% of commercials, respectively. Similarly, text or images displaying sadness, shame or covering of skin were in 40%, 45% and 30% the advertisements, respectively. None (0%) of the commercials evaluated displayed images of people scratching or verbally addressed skin itching as a bothersome symptom of psoriasis. CONCLUSIONS AND RELEVANCE: While the advertisements assessed in this study did exhibit patient concerns regarding skin appearance, skin symptoms including skin itching, flaking, pain and discomfort were not equally addressed. As these are known factors that motivate psoriasis patients to actively engage in treatment, targeted ads that better demonstrate these concerns may help prompt under-treated patients to seek care. J Drugs Dermatol. 2018;17(8):886-887.

Overview and update on biologic therapy for moderate-to-severe hidradenitis suppurativa.

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.

Comorbidities of hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is an inflammatory skin disorder with many associated comorbidities, including obesity, metabolic syndrome, smoking, depression, arthritis, autoinflammatory syndromes, inflammatory bowel disease, and genetic syndromes. In addition, HS patients can suffer from a variety of diseases related to the chronic inflammatory nature of their HS such as cardiovascular disease and anemia. An understanding of these comorbidities and associations is essential for the management of HS, and routine screening for these entities should be considered in all HS patients.