Advances in biologic and small molecule therapies for hidradenitis suppurativa

ABSTRACT

Introduction

Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disorder characterized by painful nodules, abscesses, fistulae, and scarring with a predilection for flexural regions. Several biologics and small molecule inhibitors are being evaluated in clinical trials for treatment.

Areas covered

The authors discuss the data available from clinical trials and smaller, high-quality studies for existing and emerging biologic and small molecule inhibitor therapies for treatment of HS. Biologics discussed include TNFα, IL-17, IL-23, IL-12/23, and IL-1 inhibitors. Small molecule inhibitors discussed include PDE4, JAK, TYK, IFX-1, and complement cascade inhibitors. Pharmacokinetics and pharmacodynamics for these drugs are also described.

Expert opinion

Trial data and our own experience have shown that about half of HS patients experience improvement with adalimumab. However, there is a significant need for pharmacotherapies with higher efficacy goals as in those used for psoriasis. Many biologics and small molecule inhibitors are being tested in clinical trials. The landscape of upcoming therapies for hidradenitis suppurativa appears promising.

KEYWORDS:

• Hidradenitis
• suppurativa
• biologics
• small
• molecule
• inhibitors
• therapies
• clinical
• trials
• adalimumab
• infliximab

Article highlights

• At the time of this article’s publication, adalimumab remains the only FDA-approved treatment for moderate to severe hidradenitis suppurativa. However, many biological and small molecule inhibitor therapies are in the pipeline for treatment of HS.

• Several studies have supported the efficacy of infliximab in HS. Efficacious doses are generally higher and more frequent than those used in inflammatory bowel disease.

• At the time of this article’s publication, therapies that have entered into phase III randomized clinical trials include IL-17 inhibitors (bimekizumab, secukinumab) and complement 5a receptor inhibitor (avacopan).

• Other therapies in the pipeline include IL-1 inhibitor (bermekimab), PDE4 inhibitor (orismilast), JAK inhibitor (INCB054707, upadactinib), and TYK2 inhibitor (PF-0682664).

• HS patients undergoing HS-related surgeries experience greater clinical outcomes with combination adalimumab treatment. Adalimumab should generally not be held for HS-related surgeries.

This box summarizes key points contained in the article.

Declaration of Interest

AB Kimball is a consultant and investigator for AbbVie, Janssen Pharmaceuticals, Eli Lilly and Company, Novartis, Pfizer Inc and UCB Pharma. She is also an investigator for Incyte, Bristol-Myers Squibb and Anapyts Bio. AB Kimball is also a consultant for Bayer, Ventyx, Moonlake and receives fellowship funding from Janssen Pharmaceuticals and AbbVie. AB Kimball has also been on the board of directors for the HS Foundation and the board of directors for Almirall. ML Porter meanwhile is a consultant and/or investigator for AbbVie, Janssen Pharmaceuticals, UCB Pharma, Pfizer Inc, Trifecta Clinical, Anaptys Bio, Novartis, Eli Lilly and Company and Bristol-Myers Squibb. She is also a past investigator for Chemocentryx. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.