An investigator-driven study of everolimus in surgical lung biopsy confirmed idiopathic pulmonary fibrosis

Background and objective: We evaluated the efficacy and safety of everolimus, a macrocyclic proliferation signal inhibitor with anti-fibroproliferative activity to prevent disease progression or death in patients with IPF, a progressive, fatal disease with no known effective therapy. Methods: Eighty-nine patients with surgical lung biopsy confirmed IPF were enrolled in a 3-year investigator-driven, placebo-controlled, double-blinded, multicentre study of everolimus. Results: The everolimus (n = 44) and placebo (n = 45) groups were matched for demographic variables (gender, P = 0.46) and baseline lung function parameters (FVC, P = 0.29; TLC, P = 0.45; DLCO, P = 0.41 and PaO2, P = 0.34). Independent risks for disease progression were everolimus (hazard ratio (HR) 2.37, 95% CI: 1.40-4.00, P < 0.01, log rank) and male gender (HR 2.76, 95% CI: 1.47-5.17, P < 0.01, log rank). Three-year transplant-free survival was 36 +/- 7% (everolimus) versus 51 +/- 8% (placebo) (Kaplan-Meier, P = 0.11, log rank). Independent risks for transplant-free survival were male gender (HR 2.33,95% CI: 1.07-5.05, P = 0.03, log rank) and baseline DLCO (% predicted) (HR 0.96, 95% CI: 0.93-0.99, P = 0.02, log rank). Conclusions: Everolimus use was associated with more rapid disease progression in a well-defined cohort of patients with IPF confirmed by surgical lung biopsy followed for 3 years.