Adalimumab, Ustekinumab, and Secukinumab in the Management of Hidradenitis Suppurativa: A Review of the Real-Life Experience

Clinical Cosmetic and Investigational Dermatology, Journal Year: 2023, Volume and Issue: Volume 16, P. 135 - 148

Published: Jan. 1, 2023

Abstract: To date, adalimumab (ADA) is the only biotechnology drug approved for management of hidradenitis suppurativa (HS), an inflammatory skin condition. However, it quickly became apparent that efficacy in daily practice was highly variable. In our review, we highlighted current evidence from literature on use biologics HS a real-life setting, particularly adalimumab, secukinumab and ustekinumab. Data effectiveness safety biologic drugs have been analyzed. Even if results are promising, more studies needed. opinion, armamentarium increasing, treatment will be based tailored-tail approach, minimizing risk adverse events. this context, want to point out reported data concerning ustekinumab as well ixekizumab. Keywords: suppurativa, ustekinumab, secukinumab, ixekizumab, guselkumab, real life

Language: Английский

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

JDDG Journal der Deutschen Dermatologischen Gesellschaft, Journal Year: 2024, Volume and Issue: 22(6), P. 868 - 889

Published: May 21, 2024

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

Language: Английский

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IL-1 Family Antagonists in Mouse and Human Skin Inflammation

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: March 16, 2021

Interleukin (IL)-1 family cytokines initiate inflammatory responses, and shape innate adaptive immunity. They play important roles in host defense, but excessive immune activation can also lead to the development of chronic diseases. Dysregulated IL-1 signaling is observed a variety skin disorders. In particular, have been linked pathogenesis psoriasis atopic dermatitis. The biological activity pro-inflammatory agonists controlled by natural receptor antagonists IL-1Ra IL-36Ra, as well regulatory IL-37 IL-38. These four anti-inflammatory members are constitutively highly expressed at steady state epidermis, where keratinocytes major producing cell type. this review, we provide an overview current knowledge concerning their biology inflammation therapeutic potential human We further highlight some common misunderstandings less well-known observations, which persist field despite recent extensive interest for these cytokines.

Language: Английский

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Vulvar Lichen Sclerosus from Pathophysiology to Therapeutic Approaches: Evidence and Prospects

Biomedicines, Journal Year: 2021, Volume and Issue: 9(8), P. 950 - 950

Published: Aug. 3, 2021

Vulvar lichen sclerosus (VLS) is a chronic, distressing, inflammatory disease with an enormous impact on quality of life. Treatment goals are relieving symptoms, reversing signs and preventing anatomical changes. Despite the availability numerous therapeutic options, treatment outcome may not be entirely satisfactory definitive cure does exist. This due to fact that exact VLS etiopathogenesis remains unknown. The objectives this paper were review most up-to-date knowledge consider available therapies through lens plausible pathogenetic model. An electronic search both its was performed using National Library Medicine PubMed database. Based current knowledge, it conceivable various, heterogeneous environmental factors acting genetic background trigger autoimmune, Th-1 response, which leads chronic state. This, in turn, can determine tissue micro-vascular injury activation signaling pathways involved fibroblast collagen metabolism. sequence explain effectiveness anti-inflammatory treatments, mostly topical corticosteroids, improving clinical-pathological Further deepening will presumably allow key mediators become new targets optimize treatments.

Language: Английский

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Microbiome and Probiotics in Acne Vulgaris—A Narrative Review

Life, Journal Year: 2022, Volume and Issue: 12(3), P. 422 - 422

Published: March 15, 2022

Acne vulgaris is a chronic disease characterised by the appearance of eruptions such as whiteheads, blackheads, pustules, papules, and cysts. Among factors that cause acne are abnormal keratinisation sebaceous canal, bacterial colonisation (Cutibacterium acnes), increased sebum production, genotypic factors, hormonal disorders. Treatment often long tedious, can lead to reduction in quality life social isolation. The intestinal microbiota greatly important formation lesions. It also responsible for proper immunity organism. be related condition digestive tract its microbiome. Research shows use probiotics may reduce skin eruptions. probiotic supplementation cosmetics markets very dynamically developing. internal probiotic-containing gives hope improvement people with acne.

Language: Английский

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Innate immunity and microbial dysbiosis in hidradenitis suppurativa – vicious cycle of chronic inflammation

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 28, 2022

Hidradenitis Suppurativa (HS) is a chronic multifactorial inflammatory skin disease with incompletely understood mechanisms of pathology. HS characterized by aberrant activation the innate immune system, resulting in pathways that aim to protect against pathogenic microorganisms, and also contribute failure resolve inflammation. Imbalance immunity evident deregulation host antimicrobial peptides (AMPs) complement system associated microbiome dysbiosis. The pathology further complicated ability pathogens overcome response. Potential roles major AMPs, cathelicidin, defensins, dermcidin, S100 proteins, RNAse 7 proteins are discussed. Dysregulated expression pattern components conjunction bacterial component warrants consideration novel treatment approaches targeting both HS.

Language: Английский

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Hidradenitis Suppurativa: A Perspective on Genetic Factors Involved in the Disease

Biomedicines, Journal Year: 2022, Volume and Issue: 10(8), P. 2039 - 2039

Published: Aug. 21, 2022

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease of the pilosebaceous unit, clinically consisting painful nodules, abscesses, and sinus tracts mostly in, but not limited to, intertriginous areas. HS can be defined as complex with multifactorial etiologies, including-among others-genetic, immunologic, epigenetic, environmental factors. Based on genetic heterogeneity complexity, three different forms recognized considered separately sporadic, familial, syndromic. To date, several variants associated to susceptibility, disease-onset, and/or treatment response have been reported; some these reside in genes encoding gamma-secretase subunits whereas others involve autoinflammatory keratinization genes. The aim this perspective work provide an overview contribution studies encompassing family linkage analyses, target candidate gene studies, -omic field. In our viewpoint, we discuss role genetics suppurativa considering findings based Sanger sequencing well more recent Next Generation Sequencing (i.e., exome or RNA Sequencing) better understanding etio-pathogenesis identifying novel therapeutic strategies.

Language: Английский

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Aquaporins Are One of the Critical Factors in the Disruption of the Skin Barrier in Inflammatory Skin Diseases

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 4020 - 4020

Published: April 5, 2022

The skin is the largest organ of human body, serving as an effective mechanical barrier between internal milieu and external environment. widely considered first-line defence with essential function in rejecting pathogens preventing mechanical, chemical, physical damages. Keratinocytes are predominant cells outer layer, epidermis, which acts a water-permeability barrier. epidermis permanently renewed tissue where undifferentiated keratinocytes located at basal layer proliferate migrate to overlying layers. During this migration process, undertake differentiation program known keratinization process. Dysregulation process can result series disorders. In context, aquaporins (AQPs), family membrane channel proteins allowing movement water small neutral solutes, emerging important players physiology diseases. Here, we review role AQPs keratinization, hydration, proliferation, retention, repair, wound healing, immune response activation. We also discuss dysregulated involvement some common inflammatory dermatological diseases characterised by disruption.

Language: Английский

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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

Journal of the American Academy of Dermatology, Journal Year: 2023, Volume and Issue: 90(3), P. 521 - 529

Published: Oct. 21, 2023

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

Language: Английский

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Proof-of-concept study exploring the effect of spesolimab in patients with moderate-to-severe hidradenitis suppurativa: a randomized double-blind placebo-controlled clinical trial

British Journal of Dermatology, Journal Year: 2024, Volume and Issue: 191(4), P. 508 - 518

Published: April 5, 2024

Abstract Background Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with considerable burden. Existing treatment options are limited and often suboptimal; high unmet need exists for effective targeted therapies. Objectives To explore the effects of spesolimab in patients HS. Methods This randomized double-blind placebo-controlled proof-of-clinical-concept (PoCC) study was conducted at 25 centres across 12 countries from 3 May 2021 to 21 April 2022. Patients had moderate-to-severe HS ≥ 1 year before enrolment. were (2 : 1) receive loading dose 3600-mg intravenous (1200 mg weeks 0, 2) or matching placebo, followed by maintenance either 1200-mg subcutaneous every 2 4 10 placebo. The primary endpoint percentage change baseline total abscess nodule (AN) count week 12. Secondary endpoints absolute International Suppurativa Severity Score System (IHS4), draining tunnel (dT) count, proportion achieving dT revised Area Index (HASI-R), Clinical Response (HiSCR50), flare (all 12) patient-reported outcomes. Results In this completed trial, (n = 52) received 35) placebo 17). difference vs. least squares mean reported. At 12, AN similar between arms: –4.1% [95% confidence interval (CI) –31.7 23.4]. There greater numerical improvement arm, as measured IHS4 (13.9, 95% CI –25.6 –2.3); (–96.6%, –154.5 –38.8); 0 (18.3%, –7.9 37.5). Spesolimab also improved HASI-R HiSCR50 demonstrated favourable safety profile, that observed trials other diseases. Conclusions exploratory PoCC supports development new therapeutic option

Language: Английский

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