TNF-α inhibitors in the treatment of hidradenitis suppurativa

Abstract

Hidradenitis suppurativa (HS) is a complex disease with a dramatic impact on the quality of life of patients that it afflicts. Despite this, there are few treatment options offering long-term relief. The exact pathophysiology of HS is unclear, although the current theory involves follicular obstruction, rupture, and subsequent inflammation leading to fistula and abscess development in intertriginous skin. Several inflammatory modulators have been implicated in the development of HS, including tumor necrosis factor (TNF)-α as well as interleukin (IL)-1β, IL-10, and IL-17. Initial evidence for the use of TNF-α inhibitors in HS stemmed from recognition that inflammatory bowel disease patients treated with these medications saw a concurrent improvement in their HS symptoms. Early case reports and case series illustrated TNF-α inhibitors’ value in the treatment of HS. Later, two phase III clinical trials, PIONEER I and PIONEER II, demonstrated that adalimumab is an efficacious treatment for HS. Infliximab represents another effective HS treatment option with its main advantage being dosing flexibility. In contrast, clinical trials have failed to show evidence for application of etanercept in HS. There is limited data on other TNF-α inhibitors such as certolizumab-pegol and golimumab. This review outlines the history, dosing, response, and adverse effects of TNF-α inhibitors in the treatment of HS.

A Systematic Review of Promising Therapeutic Targets in Hidradenitis Suppurativa: A Critical Evaluation of Mechanistic and Clinical Relevance

“…TNF-a is a highly pleiotropic proinflammatory cytokine, playing essential roles especially in tissue immune cell infiltration, T-cell functional polarization, systemic inflammation, and metabolic alterations, all being relevant to HS (Beutler and Cerami, 1989). TNF-a inhibition has been demonstrated to modulate T helper (Th) 17 activity (Jiménez-Gallo et al, 2018), and the use of TNF-a inhibitors (such as Adalimumab and Infliximab) demonstrate clinical efficacy in clinical trials (Savage et al, 2019).…”

Cytokine Pathways and Investigational Target Therapies in Hidradenitis Suppurativa

“…TNF-α levels exhibited a positive correlation with HS severity and the therapeutic efficacy of TNF-α inhibitors supports the role of the dysregulated production of these cytokines in the pathophysiology of HS [ 77 , 78 ]. The only Food and drug administration-approved drug available to treat HS is adalimumab, a monoclonal antibody targeting TNF-α.…”

“…Two large double-blind, placebo-controlled, randomized clinical trials (RCTs), PIONEERI and II, demonstrated the safety and efficacy of adalimumab. In these studies, patients received either adalimumab (160 mg at week 0, 80 mg at week 2, and 40 mg weekly starting at week 4) or placebo for 12 weeks [ 78 , 110 ]. The primary endpoint in both studies was the number of patients achieving clinical response according to the Hidradenitis Suppurativa Clinical Response (HiSCR) at week 12 defined as a 50% decrease in total abscess and inflammatory nodule lesions from baseline.…”

Certolizumab pegol for hidradenitis suppurativa: Case report and literature review

“…Little data on HS treated with certolizumab pegol have been published. 6,7 Certolizumab pegol offers an alternative for other anti-TNFinhibitors in pregnant patients, due to its inability to cross the placenta, 8 which to our knowledge has only been examined in a single patient. 9 Our literature review identified only a single retrospective study by Sand et al 7 on off-label use of TNF-inhibitors, which showed no efficacy from certolizumab pegol in two patients earlier treated with infliximab and adalimumab, respectively.…”

“…Little data on HS treated with certolizumab pegol have been published 6,7 . Certolizumab pegol offers an alternative for other anti‐TNF‐inhibitors in pregnant patients, due to its inability to cross the placenta, 8 which to our knowledge has only been examined in a single patient 9 .…”