Metabolic, pharmacokinetic, and toxicological issues of biologic therapies currently used in the treatment of hidradenitis suppurativa

ABSTRACT

Introduction

Hidradenitis suppurativa is a chronic, relapsing, debilitating inflammatory dermatologic disease of the terminal hair follicles at intertriginous sites clinically characterized by painful inflammatory nodules, abscesses, draining sinus tracts, and dermal fibrosis. The management of hidradenitis suppurativa is a challenge and usually consists of both medical and surgical approaches, which must often be combined for best outcome. The introduction of biological therapies, specifically TNFα-inhibitors such as adalimumab, has profoundly changed the therapeutic armamentarium of the disease.

Areas covered

The PubMed database was searched using combinations of the following keywords: hidradentis suppurativa, biologic therapy, TNF-α inhibitors, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, adverse effects, pharmacodynamics, pharmacology, adverse events, pharmacokinetics, drug interaction. This article reviews and updates the chemistry, pharmacokinetics, mechanism of action, adverse effects, drug interactions of on-label and off-label use of TNF-α inhibitors in HS.

Expert opinion

Biologic agents, particularly adalimumab, exhibit clinical efficacy in patients with hidradenitis suppurativa. Careful patient selection and close monitoring during treatment are mandatory to provide safe and effective use of the TNF-α inhibitor. Familiarity with biologic agents is crucial because these agents could become a consolidated treatment option in the clinician’s therapeutic approaches.

KEYWORDS:

• Adverse events
• hidradenitis suppurativa
• biologic agent
• tnf-α inhibitors
• adalimumab
• infliximab
• pharmacodynamics
• pharmacokinetics
• pharmacology
• toxicology

Article highlights

• Hidradenitis suppurativa is a chronic, debilitating dermatosis with occurrence of suppurative lesions, sinus tracks and scarring. Pathogenesis is multifactorial and a pilosebaceous unit occlusion, hyperkeratinization, bacterial superinfection, and immune dysregulation play a key role.

• TNF-α has a central role in the pathogenesis of hidradenitis suppurativa. Increased levels of TNF-α were found both in blood and skin lesions of patients suffering from hidradenitis suppurativa.

• Adalimumab is the only biologic agent approved by EMA and FDA for the management of moderate-to-severe hidradenitis suppurativa. In randomized, double-blind, placebo-controlled trials, including one multicenter study, adalimumab resulted as effective and well-tolerated agent, at a dosage of 40 mg every week.

• Infliximab is considered a second-line therapy in recalcitrant and adalimumab no responder patients with hidradenitis suppurativa. The optimal dosage is not established.

The limited available evidence does not support etanercept or other TNFα inhibitors for the management of hidradenitis suppurativa.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.