Clinical Implementation of Biologics and Small Molecules in the Treatment of Hidradenitis Suppurativa

Abstract

Hidradenitis suppurativa (HS) is a chronic, recurrent, auto-inflammatory skin disease originating from the hair follicles. The typical inflammatory nodules, abscesses, and draining sinus tracts (tunnels) are characterized by a massive influx of neutrophils, macrophages, B-cells, plasma cells, T helper (Th)1, Th17 cells and upregulation of pro-inflammatory cytokines such as IL-1, IL-17, IL-12/23, and TNF-α. Over the last decades, several clinical trials evaluated the clinical efficacy of different biologics targeting these pro-inflammatory cytokines, in particular TNF-α and IL-1. However, adalimumab is still the only registered drug for HS. This review discusses biologics and small molecules with high level of evidence for their clinical application, provides guidance on when and how to use these biologics and small molecules in clinical practice, and elaborates on the combination with medical and surgical treatment options beyond the current guidelines. Furthermore this review provides an overview of potential biologics and small molecules currently under investigation for novel targets in HS such as IL-36, C5a, Janus kinase family members, CD-40, LTA4 and CXCR1/2.

New and Emerging Targeted Therapies for Hidradenitis Suppurativa

“…After activation, STATs enter the nucleus to bind to transcriptional regulatory sites of target genes, and induce inflammation. Several studies evaluated the efficacy of JAK inhibitors in HS [ 172 ].…”

“…IRAK4 functions downstream of multiple innate immune cell receptors, such as TLR and IL-1Rs [ 172 ].…”

“…KT-474 is an orally administered small molecule that targets IRAK4, and is under development for the treatment of interleukin-1 receptor (IL-1R)/ TLR-driven inflammatory diseases [ 172 ]. A phase I study (NCT04772885) is currently underway, and is going to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of KT-474 in patients with HS or atopic dermatitis (AD) [ 178 ].…”

“…PF-06650833 is an IRAK4 inhibitor [ 172 ] investigated in a phase II study (NCT04092452) among participants with moderate to severe HS, which assessed the safety and efficacy of three kinase inhibitors (PF-06650833, PF-06700841, and PF-06826647) [ 179 ].…”

“…Signals from cytokines IL-23, IL-12, and type I interferons activate TYK2 [ 172 ]. Ropsacitinib (PF-06826647) is a tyrosine kinase 2 (TYK2) inhibitor [ 172 ] and a part of the above-mentioned phase II study with three kinase inhibitors (NCT04092452) [ 179 ]. Except for HS, it is being investigated for psoriasis and ulcerative colitis [ 39 ].…”