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

Abstract

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.

• Authors: James P Utz, Andrew H Limper, Sanjay Kalra, Ulrich Specks, John P Scott, Zvezdana Vuk-Pavlovic, Darrell R Schroeder
• Journal: Chest (Chest) Vol. 124 Issue 1 Pg. 177-85 (Jul 2003) ISSN: 0012-3692 [Print] United States
• PMID: 12853521 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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