Detection of native, activated Notch receptors in normal human apocrine‐bearing skin and in hidradenitis suppurativa DOI Creative Commons
Siri Hansen Stabell, Anastasia Renzi,

Hogne Røed Nilsen

et al.

Experimental Dermatology, Journal Year: 2023, Volume and Issue: 33(1)

Published: Dec. 7, 2023

Abstract Notch signalling has generated considerable interest as a pathogenetic factor and drug target in range of human diseases. The gamma‐secretase complex is crucial the activation receptors by cleaving intracellular domain allowing nuclear translocation. In recent years several mutations components have been discovered patients with familial hidradenitis suppurativa (HS). This led to hypotheses that impaired could be an important driver for HS general, not only monogenic variants. However, no study examined situ per se HS, some reports conflicting results instead based on expression or indirect measures gene expression. this we established immunostaining protocols identify native, activated skin tissue. ability detect changes was confirmed ex vivo organ model which signal reduced obliterated tissue exposed inhibitor. Using these methods biopsies from healthy volunteers general cohort demonstrated first time distribution active apocrine‐bearing skin. Quantification NOTCH1 & NOTCH2 revealed similar levels non‐lesional peri‐lesional controls, thus ruling out defect patients. We did find variable but significant reduction epidermis lesional appeared related extent surrounding inflammation.

Language: Английский

Therapeutic Potential of IL-1 Antagonism in Hidradenitis Suppurativa DOI Creative Commons
Laura Calabrese,

Dalma Malvaso,

Giulia Coscarella

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 175 - 175

Published: Feb. 1, 2024

The immunopathogenesis of HS is partially understood and exhibits features an autoinflammatory disease; it associated with the potential involvement B cells contribution Th1 or Th17 cell subsets. Recently, pathogenic role both innate immunity IL-1 family cytokines in has been deeply investigated. Several agents targeting pathway at different levels are currently available under investigation for treatment HS. still characterized by unmet clinical needs represents expanding field current scientific research. aim this narrative review to describe pathological dysregulation members provide update on therapeutic strategies cytokine signaling. Further preclinical data may likely lead enrichment armamentarium antagonists.

Language: Английский

Citations

9
IL-17 in wound repair: bridging acute and chronic responses DOI Creative Commons
Xingrui Mu,

Rifang Gu,

Ming Tang

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 27, 2024

Abstract Chronic wounds, resulting from persistent inflammation, can trigger a cascade of detrimental effects including exacerbating inflammatory cytokines, compromised blood circulation at the wound site, elevation white cell count, increased reactive oxygen species, and potential risk bacterial infection. The interleukin-17 (IL-17) signaling pathway, which plays crucial role in regulating immune responses, has been identified as promising target for treating skin diseases. This review aims to delve deeper into pathological molecular mechanisms IL-17 family its pathways repair. intricate interactions between other cytokines will be discussed detail, along with activation various pathways, provide comprehensive understanding IL-17’s involvement chronic inflammation

Language: Английский

Citations

8
Hidradenitis suppurativa, from basic science to surgery and a new era of tailored targeted therapy: An expert opinion paper DOI Creative Commons
Angelo Valerio Marzano, Michele Bartoletti, Vincenzo Bettoli

et al.

Archives of Dermatological Research, Journal Year: 2025, Volume and Issue: 317(1)

Published: Feb. 28, 2025

Abstract Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterised by an aberrant activation of innate immunity and increased production pro-inflammatory mediators such as interleukin 17 (IL-17). IL-17 has been shown to play key role in the pathogenesis HS evidence highlights potential IL-17-targeted therapies. The fully human IgG/κ monoclonal antibody secukinumab, which specifically targets IL-17A inhibits interaction with its receptor, recently approved for treatment moderate-to-severe HS. Secukinumab offers patients efficacious well-tolerated option terms sustained response rapidly improving signs symptoms, preventing progression absence loss response. Being challenging disease, associated delay diagnosis 3–10 years and, consequently, late implementation appropriate treatment, leading progression. Misdiagnosis due flawed understanding lack awareness among medical providers considered important factor contributing delayed diagnosis. Thus, serious efforts must be made on large scale urgently reduce burden patients, including raising awareness, education programmes at specialisation schools, well continuous healthcare different levels early detection initiation treatment. Here, we present main critical unmet needs affected HS, address how comprehensive multidisciplinary management (offering both surgical care) can benefit suggest therapeutic options, based clinical characterisation identification intervention (window opportunity), adopted timely better fill current gaps.

Language: Английский

Citations

0
Efficacy and safety of biologics for hidradenitis suppurativa: A network meta‐analysis of phase III trials DOI Creative Commons
Laura Calabrese, Alessandra Cartocci, Pietro Rubegni

et al.

Journal of the European Academy of Dermatology and Venereology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Phase III clinical trials are designed to evaluate the therapeutic effect of drugs and their superiority over other treatment methods, but biologics for hidradenitis suppurativa (HS) have not been compared head-to-head in phase studies. To relative efficacy safety HS a network meta-analysis including available data from trials. MEDLINE Embase were searched investigating and/or at least one biologic moderate-to-severe HS. The odds ratios reaching an Clinical Response 50 (HiSCR50) occurrence adverse events after 12-16 weeks between treatments. PIONEER I II (adalimumab 40 mg weekly vs. placebo), SUNSHINE SUNRISE (secukinumab 300 every 2 4 placebo) as well BE HEARD (bimekizumab 320 with 2731 patients included. Adalimumab was ranked most effective HiSCR50 significant secukinumab (OR = 1.74; 95% confidence interval [CI]: 1.11-2.73) 1.72; CI: 1.09-2.7) insignificant bimekizumab 1.23; 0.74-2.06) 1.25; 0.73-2.14). showed fewest 0.52; 0.32-0.86) 0.79; 0.47-1.33) 0.69; 0.45-1.07) 0.71; 0.46-1.1). Among currently approved agents HS, adalimumab demonstrated highest first treatment.

Language: Английский

Citations

0
The Role of IL-17 in Systemic Autoinflammatory Diseases: Mechanisms and Therapeutic Perspectives DOI
Jingyuan Zhang, Min Shen

Clinical Reviews in Allergy & Immunology, Journal Year: 2025, Volume and Issue: 68(1)

Published: March 12, 2025

Language: Английский

Citations

0
The preclinical discovery and development of secukinumab for the treatment of moderate-to-severe hidradenitis suppurativa DOI
Klaudia Knecht-Gurwin, Łukasz Matusiak, Jacek C. Szepietowski

et al.

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Hidradenitis suppurativa (HS) is a chronic skin condition with significant impact on patient quality of life, highlighting the need for innovative therapeutic approaches. HS characterized by its chronicity; it presents in form painful nodules, abscesses, and sinus tracts or fistulas, typically localized intertriginous areas, emerging early adulthood predominantly female population. In this review, authors discuss preclinical discovery development secukinumab HS, target identification, validation, compound selection. Methodologies such as high-content screening, chemoinformatics, animal models that validate IL-17 pathway's role are explored. The transition from to clinical development, including pharmacokinetics (PK), pharmacodynamics (PD), ADME-Tox studies, elaborated. literature search was conducted using PubMed, Web Science, Scopus, UpToDate, Cochrane Library, Embase, Google Scholar, covering relevant studies published up December 2024. integration into treatment highlights critical targeting IL-17A pathway. Although efficacious safe trials, understanding secukinumab's long-term effects optimal placement remains challenging. Future research should prioritize tailored strategies align individual disease phenotypes immune profiles enhance outcomes management.

Language: Английский

Citations

0
Interleukin-17 Family DOI
Yuping Lai, Chen Dong

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Citations

0
Golimumab and certolizumab pegol for the treatment of hidradenitis suppurativa: a literature review and future perspective DOI Creative Commons
Amirhossein Heidari, Yekta Ghane, Nazila Heidari

et al.

Therapeutic Advances in Chronic Disease, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 1, 2024

Hidradenitis suppurativa (HS) is an inflammatory skin condition with underlying process. Due to the limited efficacy of available treatments, HS remains a therapeutic challenge. The safety and tumor necrosis factor-α (TNF-α) inhibitors, adalimumab, infliximab, etanercept, are well studied in this patient population, some cases, was unresponsive them. In recent years, evidence has been growing regarding application other anti-TNFs, including certolizumab pegol (CPZ) golimumab. We sought evaluate overall golimumab CPZ management HS. A comprehensive search performed on PubMed, Scopus, Web Science, Ovid Embase databases, as Google Scholar engine from initiation 31 August 2023. total nine four studies used treat HS, respectively. Individuals concomitant immune-mediated diseases, pregnant females, patients who were refractory previous treatments achieved Suppurativa Clinical Response following administration. Also, showed promise treating recalcitrant after failure such adalimumab anti-interleukin-1. can be efficacious treatment options for moderate-to-severe especially TNF adalimumab.

Language: Английский

Citations

2
Inflammasomes: emerging therapeutic targets in hidradenitis suppurativa? DOI Creative Commons
Ciara Campbell,

Jay M Mayatra,

Ashish Neve

et al.

British Journal of Dermatology, Journal Year: 2024, Volume and Issue: 191(5), P. 670 - 679

Published: June 24, 2024

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent lesions, which affect and hair follicles in intertriginous areas. HS has multifactorial aetiology resulting barrier dysfunction associated with aberrant immune activation. There increased evidence for the role of inflammasomes pathophysiology diseases, including HS. Inflammasomes are multiprotein complexes activated following exposure to danger signals, microbial ligands components damaged host cells. Inflammasome activation induces many signalling cascades subsequent cleavage proinflammatory cytokines - most notably interleukin (IL)-1β have pathogenesis. Limited immunotherapies approved treating moderate-to-severe HS, variable response rates influenced heterogeneity. represent attractive targets suppress multiple pathways IL-1β IL-17. This review aims summarize evaluate as therapeutic treatment.

Language: Английский

Citations

2
Anti-IL-17/23 Drugs for the Treatment of Moderate-to-Severe Hidradenitis Suppurativa in Patients With Concomitant Psoriasis: A Multicenter Retrospective Study DOI Creative Commons
Luigi Gargiulo, Luciano Ibba, Alessandra Narcisi

et al.

Dermatology Practical & Conceptual, Journal Year: 2024, Volume and Issue: 14(4), P. e2024250 - e2024250

Published: Oct. 30, 2024

Introduction: Psoriasis and hidradenitis suppurativa (HS) are chronic inflammatory diseases with significant overlap in their immunologic pathways, which involve cytokines such as tumor necrosis factor-alfa, interleukin (IL)-17, IL-23. Current treatment options for HS limited, only adalimumab secukinumab approved severe cases. Given the overlapping pathogenetic features between psoriasis, anti-IL-17 anti-IL-23 drugs could represent valuable treatments management of HS. Objectives: We sought to evaluate effectiveness safety patients concomitant moderate-to-severe plaque psoriasis. Methods: conducted a multicenter retrospective study 11 Italian Dermatology Units. The was evaluated by assessing percentage achieving Clinical Response (HiSCR) each week. Results: enrolled 41 at least 16 weeks follow-up, 17 them completing 52 treatment. most commonly prescribed anti-IL drug (27 patients), followed ixekizumab (5) guselkumab (5). HiSCR achieved 39%, 74.3%, 77.8% after 16, 32, weeks, respectively. No adverse events (AEs) or AEs leading discontinuation were observed during study. common AE nasopharyngitis (4 patients). Conclusion: In this real-world study, we highlight psoriasis Longer larger studies needed further long-term these affected

Language: Английский

Citations

2