IPF is a fatal disease with no approved treatment. Tumor necrosis factor-a (TNF-a) is implicated in the pathogenesis of IPF. Efficacy and safety of etanercept, a fully human soluble TNF-a receptor, were evaluated in IPF patients.
Eighty-seven patients with well-defined IPF who had evidence of disease progression participated in a prospective, randomized, double-blind, placebo controlled, parallel-group, multicenter trial (≪26>48 weeks). Patients received etanercept (25 mg subcutaneous) or placebo twice weekly. Those with severe disease (forced vital capacity predicted <45% or diffusing capacity of lung for carbon monoxide, corrected for hemoglobin predicted <25% or partial pressure of arterial oxygen <55mmHg and oxygen saturation <88% on room air (at rest) were excluded. Concomitant treatment with corticosteroids or other therapies for IPF was not allowed. Using an ANCOVA model to calculate differences between treatment groups, the three primary endpoints, FVC% predicted, DLCOC% predicted, and alveolar to arterial O2 difference P(A-aO2) difference (at rest), were analyzed as change from baseline to Week 48. Fisher’s exact test was used to compare rate of combined endpoint death or disease p! rogression between treatment groups.
No significant difference in baseline demographics or disease status was noted. Number of men/women was 59/28, mean age was 65.2 years, length of prior diagnosis was 13.6 months, and FVC % predicted was 63.4. At 48 weeks, no significant differences between treatment groups in primary and secondary endpoints were observed (Table). In a post hoc analysis, the frequency of patients who died or had disease progression (=>10% decline in FVC [L]) at the last visit, up to 14 days after last dose was 15/45 (33.3%) and 22/40 (55.0%) in etanercept and placebo groups (p=0.052). There was no significant difference in incidence or type of adverse events, serious adverse events, infections, or serious infections between treatment groups.
Although no statistical difference was found between treatment groups in predefined primary endpoints, etanercept therapy resulted in a trend toward reduced disease progression by several measures in these patients with progressive IPF.
Drs. Raghu, Lasky, Costabel, Brown, Cottin, du Bois, Thomeer, and Utz have received research grants in this Wyeth sponsored trial. Dr. McDermott is an employee of Wyeth.