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


METHODS
Prospective, open-label, phase-2 treatment trial.


METHODS
Mayo Clinic, Rochester, MN.


METHODS
Stage II or III progressive pulmonary sarcoidosis.


METHODS
Etanercept, 25 mg subcutaneously twice weekly.


METHODS
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.
Utz
James P
JP
Division of Pulmonary and Critical Care Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Limper
Andrew H
AH
Kalra
Sanjay
S
Specks
Ulrich
U
Scott
John P
JP
Vuk-Pavlovic
Zvezdana
Z
Schroeder
Darrell R
DR
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects* / Q000627:therapeutic use*; D017565:Sarcoidosis, Pulmonary / Q000188:drug therapy*; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept