Combination Therapy of Oral LDN and Topical Pentoxifylline, Rifampin, Clindamycin for Hidradenitis Suppurativa.

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease that may have profound effects on the patient's quality of life. A personalized HS combination therapy treatment was prescribed to a 54-year-old female suffering from multiple painful sores, as follows: naltrexone capsules titrated from 0.5 mg up to 4.5 mg; pentoxifylline 5%, rifampin 2%, clindamycin 1%, and glycolic acid topical cream. Clinical improvements were observed using two disease-specific outcome measures: Hurley Staging System and HS Score. The patient's HS improved from Stage II (moderate) to Stage I (mild), and the HS score decreased from 103 points with five anatomical regions reported, to 19 points with only three regions affected. Furthermore, the before and after treatment photographs showed a visible reduction in the number of boils/skin abscesses and an overall recovery. Improvements were also observed across all domains of the patient's self-reported quality of life (Hidradenitis Suppurativa Quality of Life Assessment). The patient did not experience any undesirable effects. Compounded medications may be customized to meet the patient's special needs and may be adjusted throughout the course of treatment to match the patient's individual progress. Although further studies are necessary, this personalized, combination therapy may be a key treatment option in HS.

Anti-IL17 Secukinumab in hidradenitis suppurativa: A long-term drug survival analysis.

Real-world data on the long-term effectiveness of the anti-IL17 agent secukinumab in treating moderate-to-severe Hidradenitis suppurativa (HS) are lacking. In this study, 24 patients with moderate-severe HS received five weekly subcutaneous injections followed by maintenance doses every 4 weeks. Primary outcomes included HiSCR, IHS4 reduction, and DLQI measures assessed at 12-week intervals. The median secukinumab drug survival was 16.0 months (range 3-51), with a 56.5% maximal response rate at 6 months and dropout exceeding 40% at 1 year. Baseline disease burden emerged as a key predictor of treatment response, overshadowing factors like sex or BMI. Prior systemic steroid use negatively impacts drug survival. The study underscores the critical 6-month window for assessing treatment efficacy, emphasizing the importance of initial induction dosing. Additionally, the newly developed scoring system, IHS4-55, showed analogies to the older HiSCR score in capturing treatment response. In this real-life scenario, challenges persist in HS management, necessitating innovative therapeutic approaches and predictive markers.

Comparative transcriptome analysis of acne vulgaris, rosacea, and hidradenitis suppurativa supports high-dose dietary zinc as a therapeutic agent.

Acne vulgaris, rosacea, and hidradenitis suppurativa are enduring inflammatory skin conditions that frequently manifest with akin clinical attributes, posing a considerable challenge for their distinctive diagnosis. While these conditions do exhibit certain resemblances, they also demonstrate distinct underlying pathophysiological mechanisms and treatment modalities. Delving into both the molecular parallels and disparities among these three disorders can yield invaluable insights for refined diagnostics, effective management, and targeted therapeutic interventions. In this report, we present a comparative analysis of transcriptomic data across these three diseases, elucidating differentially expressed genes and enriched pathways specific to each ailment, as well as those shared among them. Specifically, we identified multiple zinc-binding proteins (SERPINA1, S100A7, S100A8, S100A9 and KRT16) as consistently highly upregulated genes across all three diseases. Our hypothesis suggests that these proteins could bind and sequester zinc, potentially leading to localized zinc deficiency and heightened inflammation. We identified high-dose dietary zinc as a promising therapeutic approach and confirmed its effectiveness through validation in an acne mouse model.

Adherence to Hidradenitis Suppurativa Treatment.

Hidradenitis suppurativa (HS) is a chronic, debilitating skin condition that requires multimodal treatment. Adherence remains a significant challenge for many patients due to complex nature of treatment, thus presenting a barrier to management success. This review summarizes the current literature on the factors associated with adherence to medications, and lifestyle behaviors in patients with HS and proposes strategies to improve adherence. In February 2023, a systematic literature search was conducted by two independent authors on PubMed and EMBASE for articles from 2000 to 2023 on hidradenitis suppurativa adherence. A total of 21 articles met inclusion/exclusion criteria for this review. Of the studies, 11 addressed systemic medication adherence, 3 addressed topical medication adherence, 2 addressed both systemic and topical medication adherence, and 5 addressed lifestyle/behavioral modification adherence. The generalizability of results was limited by differences in study design, outcome measures, and sample size. English-only articles with full texts were used. The most reported reasons for non-adherence included presence of side effects, cost of medications, low efficacy, and unclear instructions. Proposed strategies to improve adherence in HS patients include management of side effects, use of reminder systems, improved patient education, patient support groups, aid of family and caregivers, personalization of the medication regimen, and regular follow-ups with patients. PROSPERO Registration Number: CRD42023488549.

S2k guideline for the treatment of hidradenitis suppurativa / acne inversa - Short version.

The S2k guideline on hidradenitis suppurativa/acne inversa (HS/AI) aims to provide an accepted decision aid for the selection/implementation of appropriate/sufficient therapy. HS/AI is a chronic recurrent, inflammatory, potentially mutilating skin disease of the terminal hair follicle-glandular apparatus, with painful, inflammatory lesions in the apocrine gland-rich regions of the body. Its point prevalence in Germany is 0.3%, it is diagnosed with a delay of 10.0 ± 9.6 years. Abnormal differentiation of the keratinocytes of the hair follicle-gland apparatus and accompanying inflammation form the central pathogenetic basis. Primary HS/AI lesions are inflammatory nodules, abscesses and draining tunnels. Recurrences in the last 6 months with at least 2 lesions at the predilection sites point to HS/AI with a 97% accuracy. HS/AI patients suffer from a significant reduction in quality of life. For correct treatment decisions, classification and activity assessment should be done with a validated tool, such as the International Hidradenitis Suppurativa Severity Scoring System (IHS4). HS/AI is classified into two forms according to the degree of detectable inflammation: active, inflammatory (mild, moderate, and severe according to IHS4) and predominantly inactive, non-inflammatory (Hurley grade I, II and III) HS/AI. Oral tetracyclines or 5-day intravenous therapy with clindamycin are equal to the effectiveness of clindamycin/rifampicin. Subcutaneously administered adalimumab, secukinumab and bimekizumab are approved for the therapy of HS/AI. Various surgical procedures are available for the predominantly non-inflammatory disease form. Drug/surgical combinations are considered a holistic therapy method.

The use of biologics and JAK inhibitors in the management of moderate to severe Hidradenitis Suppurativa treatment: a scoping review.

This scoping review aims to characterize the use of biologics and Janus Kinase inhibitors (JAKi) in the treatment of Hidradenitis Suppurativa (HS), which is a chronic inflammatory condition. A comprehensive literature search was conducted in PubMed/NCBI, Embase, Web of Science databases, and the Clinicaltrials.gov register. The search included interventional trials assessing the use of biologics or JAKi in HS, with no geographic or time restrictions. Secukinumab and adalimumab were identified as the only two drugs approved by the FDA for treating moderate to severe HS in adults. Several other drug classes showed promising results based on clinical studies reviewed. IL-12/23 inhibitor ustekinumab demonstrated improvements in disease severity scores and HiSCR rates in small trials. IL-17 inhibitors such as brodalumab, bimekizumab, and CJM112 showed preliminary positive responses in early-phase clinical studies and case reports. While evidence was mixed, some TNF-α inhibitors such as infliximab provided benefits according to a randomized controlled trial, though etanercept trials yielded non-significant or inconsistent findings. Larger, well-designed studies are required to further establish their efficacy and safety, but biologics and JAKis show potential as alternative treatment options for moderate to severe HS. The findings of this review contribute to the growing interest among patients and to enhancing the understanding of physician's regarding potential alternative therapeutic options for HS and provide a basis for further research in this field.

Hematologic Abnormalities in Patients With Hidradenitis Suppurativa Receiving Adalimumab.

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

Efficacy and safety of bimekizumab in patients with moderate-to-severe hidradenitis suppurativa (BE HEARD I and BE HEARD II): two 48-week, randomised, double-blind, placebo-controlled, multicentre phase 3 trials.

BACKGROUND: Patients with hidradenitis suppurativa have substantial unmet clinical needs and scarce therapeutic options. We aimed to assess the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with moderate-to-severe hidradenitis suppurativa. METHODS: BE HEARD I and II were two identically designed, 48-week randomised, double-blind, placebo-controlled, multicentre phase 3 trials. Patients aged 18 years or older with moderate-to-severe hidradenitis suppurativa were randomly assigned 2:2:2:1 using interactive response technology (stratified by worst Hurley Stage at baseline and baseline systemic antibiotic use) to receive subcutaneous bimekizumab 320 mg every 2 weeks; bimekizumab 320 mg every 2 weeks to week 16, then every 4 weeks to week 48; bimekizumab 320 mg every 4 weeks to week 48; or placebo to week 16, then bimekizumab 320 mg every 2 weeks. The primary outcome was an hidradenitis suppurativa clinical response of at least 50%, defined as a reduction in total abscess and inflammatory nodule count of at least 50% from baseline with no increase from baseline in abscess or draining tunnel count (HiSCR50) at week 16. Efficacy analyses included all randomly assigned study patients (intention-to-treat population). Safety analyses included all patients who received at least one full or partial dose of study treatment in the safety set, and of bimekizumab in the active-medication set. These trials are registered at ClinicalTrials.gov, NCT04242446 and NCT04242498, and both are completed. FINDINGS: Patients for BE HEARD I were recruited from Feb 19, 2020, to Oct 27, 2021, and 505 patients were enrolled and randomly assigned. Patients for BE HEARD II were recruited from March 2, 2020, to July 28, 2021, and 509 patients were enrolled and randomly assigned. The primary outcome at week 16 was met in the group who received bimekizumab every 2 weeks using modified non-responder imputation; higher responder rates were observed with bimekizumab versus placebo in both trials: 138 (48%) of 289 patients versus 21 (29%) of 72 patients in BE HEARD I (odds ratio [OR] 2·23 [97·5% CI 1·16-4·31]; p=0·0060) and 151 (52%) of 291 patients versus 24 (32%) of 74 patients in BE HEARD II (2·29 [1·22-4·29]; p=0·0032). In BE HEARD II, HiSCR50 was also met in the group who were administered bimekizumab every 4 weeks (77 [54%] of 144 vs 24 [32%] of 74 with placebo; 2·42 [1·22-4·80]; p=0·0038). Responses were maintained or increased to week 48. Serious treatment-emergent adverse events were reported in 40 (8%) patients in BE HEARD I and in 24 (5%) patients in BE HEARD II treated with bimekizumab over 48 weeks. The most frequently reported treatment-emergent adverse events to week 48 were hidradenitis in both trials, in addition to coronavirus infection and diarrhoea in BE HEARD I, and oral candidiasis and headache in BE HEARD II. One death was reported across the two trials, and was due to congestive heart failure in a patient with substantial cardiovascular history treated with bimekizumab every 2 weeks in BE HEARD I (considered unrelated to bimekizumab treatment by the investigator). No new safety signals were observed. INTERPRETATION: Bimekizumab was well tolerated by patients with hidradenitis suppurativa and produced rapid and deep clinically meaningful responses that were maintained up to 48 weeks. Data from these two trials support the use of bimekizumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa. FUNDING: UCB Pharma.

Brodalumab for moderate-severe hidradenitis suppurativa: An open-label multicentric cohort study in real clinical practice.

INTRODUCTION: The use of biological therapy is becoming increasingly common in patients with hidradenitis suppurativa (HS). Levels of serum TNF-alfa and IL17 support the role of an immune system dysregulation in the pathogenesis of HS. Brodalumab targets the receptor A of IL-17, thus having a promising role in the treatment of HS. MATERIAL AND METHODS: A multicenter retrospective observational open-label study was conducted in two tertiary hospitals. Adults with moderate to severe HS under treatment with brodalumab 210 mg at week 0, 1, 2 and then every 2 weeks were included and assessed at weeks 0 and 16 which was the median follow-up time. Demographic and disease-related variables as well as response parameters (HiSCR and IHS4) and safety data were recorded and analysed. RESULTS: A total of 16 patients (75% males) were included in our study. 50% of patients presented an inflammatory phenotype and mean BMI was 28.37. HiSCR was achieved in 50% of patients and mean IHS4 decreased from 24.13 to 16.81 (p = 0.002). No differences were found between those who achieved HiSCR and those who did not. Grade 2 adverse events were reported in three patients with no fatal outcomes and treatment discontinuation was advised in four patients. CONCLUSIONS: Brodalumab seems to be effective and safe in patients with moderate to severe HS, even in those that did not respond to adalimumab, which, at the moment, is the only widely approved biologic for this indication. Thus, it stands as an interesting option for the treatment of HS.

Efficacy and safety of a combined pharmacological and surgical approach in patients affected by hidradenitis suppurativa: data from a retrospective real-world clinical study.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating chronic skin disease; its therapeutic approach often requires combined medical and surgical treatment. METHODS: The aim of this study was to assess the efficacy and safety of the surgical approach combined with different pharmacological treatments, evaluating the proportion of patients achieving the hidradenitis suppurativa clinical response (HiSCR), along with the incidence of postoperative complications, and local recurrence. A retrospective study of HS patients (Hurley I-III) presenting at least one skin lesion requiring surgery was performed. Demographic and clinical data were collected (kind and anatomical location of lesion excised, type of surgical procedure). Further data included: Hurley stage and IHS4 at baseline and week 16, HiSCR at week 16 after surgery, ongoing therapy at the time of surgery (topical, systemic antibiotic, biologics), postoperative complications and local recurrence at week 16. RESULTS: Forty-two patients with female predominance (66.7%, 28/42), with a mean age of 30.3 (SD±10.5) years, were enrolled. At week 16, 53% of patients achieved HiSCR, with baseline Hurley III inversely related to HiSCR achievement (P<0.05). No increased incidence of postoperative complications was detected. Three cases of local recurrence were reported at week 16. CONCLUSIONS: The results support the efficacy and safety of the combined therapy in the management of HS; no increased risk of complications emerged among patients concomitantly treated with biologics, compared to those on conventional systemic therapy or exclusively treated with surgery.

Dermatologists' Perspectives on Biosimilars.

BACKGROUND: Biosimilars are biologic agents the Food and Drug Administration (FDA) has deemed to have no clinical difference from their reference biologics. In dermatology,  biosimilars are approved for the treatment of psoriasis and hidradenitis suppurativa. Although dermatologists are high prescribers of biologics, they are more reluctant to prescribe biosimilars than other specialists. This survey-based study sought to characterize dermatologists’ current perspectives on biosimilars.  Methods: A 27-question survey was distributed via email to dermatologists between September and October of 2022.  Results: Twenty percent of respondents would not prescribe a biosimilar for an FDA-approved indication. When asked about the greatest barriers to biosimilar adoption, 61% had concerns about biosimilar safety and efficacy, 24% reported uncertainty about state laws for interchangeability and substitutions, and 20% had concerns about biosimilar safety without concerns about efficacy. Thirty-five percent of respondents felt moderately or extremely knowledgeable about biosimilar interchangeability.  Conclusion: Biosimilars are safe and effective for treating approved dermatological conditions and may lower patient costs compared to their reference products. Patients are not always offered biosimilar therapy as an option, which may be due to unfamiliarity among dermatologists.  This survey suggests a need for more research and educational initiatives, such as modules and workshops that focus on biosimilar safety, efficacy, and interchangeability guidelines. J Drugs Dermatol. 2024;23(4):doi:10.36849/JDD.7755.

An evaluation of secukinumab for the treatment of moderate-to-severe hidradenitis suppurativa.

INTRODUCTION: Until recently, biological therapy for hidradenitis suppurativa was limited to anti-tumor necrosis factor (TNF) blockade with adalimumab (ADA). However, not all patients respond to treatment with ADA. This highlighted the need for more therapeutic options. Interleukin (IL)-17/T-helper 17 (Th17) axis may play an important role in the pathophysiology of HS. Recently, the IL-17A inhibitor secukinumab, which targets IL-17A specifically and prevents it from interacting with the IL-17 receptor, has been FDA-approved for HS. AREAS COVERED: Secukinumab, represents a novel therapeutic strategy in HS management. An overview of structural and pharmacological characteristics is provided. Described efficacy in clinical trials and case reports and safety data from is presented. EXPERT OPINION: As response to anti-TNFas is lost over time, secukinumab has provided an alternative HS treatment option in clinical practice. Overall, secukinumab has shown good efficacy and a favorable side effect profile in HS clinical trials but may be avoided in patients with inflammatory bowel disease. Long-term and real-life data on the use of secukinumab are essential for improving decision-making in HS therapy.

An Update on Current Clinical Management and Emerging Treatments in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a severe, debilitating, chronic inflammatory skin disease characterized by recurrent painful nodules, abscesses and draining sinus tracts in intertriginous areas. While this condition appears to stem from follicular unit dysfunction, its cause is multifactorial and the exact pathogenesis has yet to be fully elucidated. These factors make treatment selection challenging and contribute to variable therapeutic response among affected patients. Typical regimens consist of a combination of medical and surgical modalities, tailored to individual responses. However, HS is often refractory to traditional treatments, prompting the need for newer and more effective therapies. Herein, we review current and emerging HS therapies.