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.