Etanercept for the treatment of stage II and III progressive pulmonary sarcoidosis

James P. Utz, Andrew H. Limper, Sanjay Kalra, Ulrich Specks, John P. Scott, Zvezdana Vuk-Pavlovic, Darrell R. Schroeder

Research output: Contribution to journalArticle

287 Scopus citations

Abstract

Background: Tumor necrosis factor (TNF)-α is produced by macrophages and other cells, and is believed to participate in granulomatous inflammation. Targeted antagonism of TNF-α has been proposed as a novel treatment strategy for sarcoidosis. Etanercept is a dimeric fusion protein that binds specifically to TNF-α, rendering it biologically inactive. Objective: To assess whether etanercept has potential efficacy in the treatment of progressive pulmonary sarcoidosis. Design: Prospective, open-label, phase-2 treatment trial. Setting: Mayo Clinic, Rochester, MN. Patients: Stage II or III progressive pulmonary sarcoidosis. Intervention: Etanercept, 25 mg subcutaneously twice weekly. Measurements: Pulmonary function, chest radiographs, dyspnea, and TNF-α levels in serum and BAL fluid. Results: The study was terminated after the enrollment of 17 patients due to an early-stop clause of the pretrial study design related to excessive treatment failures. Neither absolute levels of TNF-α nor TNF-α activity in the serum, BAL fluid, or alveolar macrophages were able to predict which patients would respond to etanercept. Conclusions: In patients with progressive stage II or III pulmonary sarcoidosis, etanercept was frequently associated with early or late treatment failure. These data would not support the design of a large multicenter randomized trial comparing etanercept with conventional corticosteroid therapy.

Original languageEnglish (US)
Pages (from-to)177-185
Number of pages9
JournalChest
Volume124
Issue number1
DOIs
StatePublished - Jul 1 2003

Keywords

  • BAL
  • Etanercept
  • Sarcoidosis
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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