| 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
(Affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.)
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| Journal | Chest
(Chest)
Vol. 124
Issue 1
Pg. 177-85
(Jul 2003)
ISSN: 0012-3692 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
- TNFR-Fc fusion protein
|
| Topics |
- Anti-Inflammatory Agents, Non-Steroidal
(adverse effects, therapeutic use)
- Bronchoalveolar Lavage Fluid
(chemistry)
- 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)
|
