Etanercept in Hidradenitis Suppurativa

Overview

The rationale of the protocol is based on the reported beneficiary results of case-patients by the administration of other anti-TNF drug (infliximab) in separate cases on the grounds of a probable autoimmune predisposition of the disease. The objective of this study is to clarify the potency of etanercept for the therapy of hidradenitis suppurativa.

Hidradenitis suppurativa is a disorder of unknown etiology. Various hypotheses have implicated obesity, diabetes mellitus, genetic predisposition and tight clothing as probable contributing factors. Although patients are presenting with suppuration of their lesions, typical furuncles are absent (1). Administration of antibiotics offers transient relief of symptoms whereas therapies like androgens, isotretinoin and methotrexate have failed to disclose clinical benefit (2). More than thirty out-patients with hidradenitis suppurativa are followed up at the clinic of the "Immunology of Infectious Diseases" of the ATTIKON University Hospital of Athens. None of them is presenting with diabetes mellitus and their CD4 cell counts are within normal limits. However, their testing for the function of monocytes is often abnormal. This test involves the isolation of monocytes and the ex vivo release of pro-inflammatory cytokines both without and after stimulation by bacterial endotoxins and lipoteichoic acid. Results have shown an increased baseline secretion and poor response of monocytes after stimulation. Case reports with limited number of patients have disclosed clinical benefit of an other anti-TNF drug (infliximab) after one or two doses administration in hidradenitis suppurativa. These reports involve retrospective results of five patients (3) or single cases (4,5). The rationale of the administration of etanercept in hidradenitis suppurativa is based on the following data: a) etanercept has been proven effective for the management of psoriasis that is considered a skin disorder with autoimmune background (6); and b) laboratory findings of our patients with hidradenitis suppurativa point towards an altered immune response of their adaptive immunity (7). Tumor necrosis factor (TNF) is a dominant cytokine in the inflammatory process of rheumatoid arthritis. Elevated levels of TNF are also found in the synovium of patients with psoriatic arthritis. Etanercept is a competitive inhibitor of TNF-binding to its cell surface receptors and thereby inhibits the biological activity of TNF. TNF and lymphotoxin are pro-inflammatory cytokines that bind to two distinct cell surface receptors: the 55-kilodalton (p55) and 75-kilodalton (p75) tumor necrosis factor receptors (TNFRs). Both TNFRs exist naturally in membrane-bound and soluble forms. Soluble TNFRs are thought to regulate TNF biological activity. TNF and lymphotoxin exist predominantly as homotrimers, with their biological activity dependent on cross-linking of cell surface TNFRs. Dimeric soluble receptors such as etanercept possess a higher affinity for TNF than monomeric receptors and are considerably more potent competitive inhibitors of TNF binding to its cellular receptors. In addition, use of an immunoglobulin Fc region as a fusion element in the construction of a dimeric receptor imparts a longer serum half-life. OBJECTIVE The objective of this study is to clarify the potency of etanercept for the therapy of hidradenitis suppurativa. RATIONALE The rationale of the protocol is based on the reported beneficiary results of case-patients by the administration of other anti-TNF drug (infliximab) in separate cases on the grounds of a probable autoimmune predisposition of the disease.

Conditions

Interventions

Eligibility

Locations (1)

Outcomes