title: An investigator-driven study of everolimus in surgical lung biopsy confirmed idiopathic pulmonary fibrosis.
abstract: 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; DL(CO) , P = 0.41 and PaO(2) , 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 DL(CO) (% 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.
authors.affiliation: The Lung Transplant Unit, St. Vincent's Hospital, Sydney, New South Wales, Australia. mmalouf@stvincents.com.au
authors.forename: Monique A
authors.initials: MA
authors.lastname: Malouf
authors.forename: Peter
authors.initials: P
authors.lastname: Hopkins
authors.forename: Gregory
authors.initials: G
authors.lastname: Snell
authors.forename: Allan R
authors.initials: AR
authors.lastname: Glanville
mesh_terms: D000328:Adult; D000368:Aged; D001315:Australia; D001706:Biopsy; D018450:Disease Progression; D004311:Double-Blind Method; D000068338:Everolimus; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008168:Lung / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D012737:Sex Factors; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus