New and Emerging Targeted Therapies for Hidradenitis Suppurativa

Abstract

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease deriving from the hair follicles. The formation of inflammatory nodules, abscesses, fistulas, and sinus tracts is characterized by a large inflow of key pro-inflammatory mediators, such as IFN-γ, TNF-α, IL-1, IL-17, and IL-12/23. Adalimumab is currently the only Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved biologic therapy for moderate to severe HS in adults and adolescents. However, the long-term effectiveness of this TNF-α inhibitor in HS patients has shown to be highly variable. This review aims to review the evidence for emerging therapies that target the main pro-inflammatory cytokines in HS pathogenesis. A review of the literature was conducted, using the PubMed and Google Scholar repositories, as well as Clinicaltrials.gov. Presently, the most promising biologics in phase III trials are anti-IL-17 antibodies, secukinumab, and bimekizumab. Furthermore, an anti-IL-1 biologic, bermekimab, is currently in phase II trials, and shows encouraging results. Overall, the clinical efficacies of all new targeted therapies published up to this point are limited. More studies need to be performed to clarify the precise molecular pathology, and assess the efficacy of biological therapies for HS.

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

“…HS therapeutic options are based on disease severity and include a combination of topical and systemic therapies, including biologic drugs, surgical approach, as well as general measures and analgesics to reduce both pain and the burden of disease [ 33 ]. Topical application of clindamycin twice a day on the affected areas represents the mainstay treatment in the milder localized form of HS, whereas systemic antibiotic therapies with tetracyclines, clindamycin, and/or rifampicin in different regimens is often required to control the disease and reduce the flares in non-responders to topical therapy and moderate HS [ 26 ]; acitretin and dapsone could be employed as an alternative to, or in combination with, antibiotic therapy in mild-to-moderate HS [ 26 ].…”

“…Topical application of clindamycin twice a day on the affected areas represents the mainstay treatment in the milder localized form of HS, whereas systemic antibiotic therapies with tetracyclines, clindamycin, and/or rifampicin in different regimens is often required to control the disease and reduce the flares in non-responders to topical therapy and moderate HS [ 26 ]; acitretin and dapsone could be employed as an alternative to, or in combination with, antibiotic therapy in mild-to-moderate HS [ 26 ]. Adalimumab, an antagonist of TNF (Tumor Necrosis Factor)-α, is the only approved biologic drug for moderate-to-severe HS, with a significant improvement ranging from 41.8% to 77% of treated patients, as shown in clinical trials and real-life observational studies [ 33 ]; the evidence of a “window of opportunity” supports the early use of adalimumab in HS to ensure better clinical response [ 34 ]. Surgical treatments (e.g., deroofing, incision and draining, local excision of the lesions) are taken into account in the most severe stage of HS with extensive and long-standing sinus tracts/fistulae formation or in treatment-refractory disease [ 35 ].…”

“…Smoking cessation, weight reduction, avoidance of triggers factors (friction, rubbing, sweating) in apocrine-bearing areas are accepted general measures to reduce exacerbation and ensure a better quality of life, especially in the milder forms of disease [ 35 ]. An extensive review on HS current treatment options and ongoing clinical trials has been recently published by Markota Čagalj et al [ 33 ]; however, despite the great number of emerging treatments, the burden of the disease remains high, and long-lasting impairment of the patients’ quality of life has been reported [ 36 ]. Finally, no guidelines are currently available for different HS clinical phenotypes and its syndromic forms; thus, extensive, basic, and molecular research is still required to fully unravel the various mechanisms underlying this disease [ 36 ].…”

Current Medical and Surgical Treatment of Hidradenitis Suppurativa—A Comprehensive Review

“…Adalimumab, a fully human, IgG1 monoclonal antibody specific for TNFα, is currently the only biologic therapy approved for the treatment of moderate-to-severe HS in adults and adolescent patients ≥12 years ( Table 4 ) [ 20 , 22 , 112 ]. In two phase III multicenter, double-blind, placebo-controlled studies (PIONEER I and PIONEER II) adalimumab showed a significant effectivity compared to placebo with HiSCR rates of 41.8% and 58.9% (vs. 26.0% and 27.6% in placebo groups), respectively [ 113 ].…”

The complement system and its role in the treatment of ANCA-associated vasculitis

“…Obecnie prowadzone są również badania nad zastosowaniem Avacopan w leczeniu trądziku odwróconego 12 oraz roli terapii celowanej w receptor C5a w leczeniu immunosupresji w posocznicy. 13 Ponadto Avacopan może w przyszłości posłużyć jako inhibitor granulocytów w leczeniu pacjentów z toczniem rumieniowatym układowym.…”