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

Chest. 2003 Jul;124(1):177-85. doi: 10.1378/chest.124.1.177.


Background: Tumor necrosis factor (TNF)-alpha is produced by macrophages and other cells, and is believed to participate in granulomatous inflammation. Targeted antagonism of TNF-alpha has been proposed as a novel treatment strategy for sarcoidosis. Etanercept is a dimeric fusion protein that binds specifically to TNF-alpha, 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-alpha 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-alpha nor TNF-alpha 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / adverse effects*
  • Immunoglobulin G / therapeutic use*
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Recombinant Fusion Proteins / adverse effects*
  • Recombinant Fusion Proteins / therapeutic use*
  • Sarcoidosis, Pulmonary / drug therapy*
  • Treatment Failure
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
  • Etanercept