Clinical efficacy of complement C5a inhibition by IFX‐1 in hidradenitis suppurativa: an open‐label single‐arm trial in patients not eligible for adalimumab

Giamarellos‐Bourboulis, Evangelos J.; Argyropoulou, Maria D.; Kanni, Theodora; Spyridopoulos, Theodoros; Otto, Isabella; Zenker, O.; Guo, Ruocheng; Riedemann, Niels C.

doi:10.1111/bjd.18877

Cited by 49 publications

(55 citation statements)

References 6 publications

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“…The inflammatory signature of established hidradenitis suppurativa has been well characterized in multiple histologic 26,41 and molecular studies. 26,[42][43][44][45] Similarities and parallels with psoriasis 26 have been observed in lesional and perilesional hidradenitis suppurativa tissue, 26,46 with lesional nodules demonstrating mixed inflammatory infiltrates comprising T cells, dendritic cells, plasma cells, neutrophils, [47][48][49][50] and monocytes. 51 Chronic long-…”

Section: Inflammation In Hidradenitis Suppurativa: Evidence From Exismentioning

confidence: 75%

Hidradenitis suppurativa is an autoinflammatory keratinization disease: A review of the clinical, histologic, and molecular evidence

Frew

2020

JAAD International

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The pathogenic model of hidradenitis suppurativa is in the midst of a paradigm shift away from a disorder of primary follicular occlusion to an autoinflammatory keratinization disease. Observational, experimental, and therapeutic evidence supports the concept of hidradenitis suppurativa as a primarily inflammatory disorder, a disorder of autoimmunity, or both, in contrast to the current prevailing paradigm of primary follicular occlusion. The lack of reliable and high-fidelity disease models has limited the available experimental and mechanistic evidence to support or refute one pathogenic model over another. This scholarly review synthesizes the existing clinical, histologic, and molecular data to evaluate the extant evidence supporting the autoinflammatory paradigm and further informing the molecular mechanisms of hidradenitis suppurativa pathogenesis. Follicular hyperkeratosis/occlusion and perifollicular inflammation coexist in histologic specimens, with interleukin 1a demonstrated to stimulate comedogenesis in the infundibulum. pH elevation in occluded body sites alters the microbiome and amplifies existing T-helper cell type 17 immunoresponses. Known metabolic comorbidities and smoking are known to upregulate interleukin 1a in follicular keratinocytes. Identified genetic variants may alter epidermal growth factor receptor signaling, leading to upregulated keratinocyte inflammatory responses. The process of follicular rupture and dermal tunnel formation can be explained as secondary responses to inflammatory activation of fibroblasts and epithelial-mesenchymal transition, with antibody production associated with inflammatory amplification in advanced disease. This review aims to reevaluate and integrate the current clinical, histologic, and molecular data into a pathogenic model of hidradenitis suppurativa. This is essential to advance our understanding of the disease and identify novel therapeutic targets and approaches.

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Section: Inflammation In Hidradenitis Suppurativa: Evidence From Exismentioning

confidence: 75%

Hidradenitis suppurativa is an autoinflammatory keratinization disease: A review of the clinical, histologic, and molecular evidence

Frew

2020

JAAD International

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“…Furthermore, this same study identified increased levels of autoantibodies recognizing citrullinated peptides and NET antigens ( 10 ). A recently published clinical trial using an IgG5 monoclonal antibody that selectively binds to C5a and blocks its biological activity demonstrated modest clinical efficacy in HS ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis

Gudjonsson¹,

Tsoi²,

Ma³

et al. 2020

JCI Insight

136

137

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Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus tracts in the groin, axillae, and perineum. Using proteomic and transcriptomic approaches, we characterized the inflammatory responses in HS in depth, revealing immune responses centered on IFN-γ, IL-36, and TNF, with lesser contribution from IL-17A. We further identified B cells and plasma cells, with associated increases in immunoglobulin production and complement activation, as pivotal players in HS pathogenesis, with Bruton’s tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) pathway activation as a central signal transduction network in HS. These data provide preclinical evidence to accelerate the path toward clinical trials targeting BTK and SYK signaling in moderate-to-severe HS.

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“…IFX-1 is a human C5a-specific monoclonal antibody [ 31 , 146 ]. An open-label clinical trial reported that 75% of patients achieved HiSCR at day and more than 80% at day 134 [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

Cytokine Pathways and Investigational Target Therapies in Hidradenitis Suppurativa

Duca

Morelli

Bennardo

et al. 2020

IJMS

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Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting areas with a high density of apocrine glands and characterized by subcutaneous nodules that may evolve into fistulas with pus secretion. Methods: The aim of this review is to investigate all current knowledge on cytokine regulation in the pathogenesis of HS. A systematic literature research using the words “cytokine”, “interleukin”, “pathway”, and “hidradenitis suppurativa” was performed in PubMed/Medline and Scopus/Embase databases. A search of the clinicaltrials.gov website for interventional recruiting and completed trials including the term “hidradenitis suppurativa” was also performed up to August 2020. We will discuss the pathogenetic role of various cytokines in HS and potential therapeutic targets for this debilitating disease. Results: The pathophysiology underlying this complex condition has not been clearly defined. An upregulation of various cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, IL-17, IL-23, and other molecules seems to be related to this inflammatory condition. Various cells, such as lymphocytes T Helper 1 and 17 and keratinocytes seem to be involved in the genesis of this condition. Conclusions: Several future studies and clinical trials are necessary in order to have new knowledge about HS and to properly treat this complex condition.

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Clinical efficacy of complement C5a inhibition by IFX‐1 in hidradenitis suppurativa: an open‐label single‐arm trial in patients not eligible for adalimumab

Cited by 49 publications

References 6 publications

Hidradenitis suppurativa is an autoinflammatory keratinization disease: A review of the clinical, histologic, and molecular evidence

Hidradenitis suppurativa is an autoinflammatory keratinization disease: A review of the clinical, histologic, and molecular evidence

Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis

Cytokine Pathways and Investigational Target Therapies in Hidradenitis Suppurativa

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