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; 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.
RCT Entities:
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; 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: Natalie M Walker; Elizabeth A Belloli; Linda Stuckey; Kevin M Chan; Jules Lin; William Lynch; Andrew Chang; Serina M Mazzoni; Diane C Fingar; Vibha N Lama Journal: J Biol Chem Date: 2016-01-11 Impact factor: 5.157
Authors: Keith T Ferguson; Elizabeth E Torr; Ksenija Bernau; Jonathan Leet; David Sherris; Nathan Sandbo Journal: J Cell Biochem Date: 2017-04-18 Impact factor: 4.429
Authors: Erin M O'Leary; Yufeng Tian; Recep Nigdelioglu; Leah J Witt; Rengul Cetin-Atalay; Angelo Y Meliton; Parker S Woods; Lucas M Kimmig; Kaitlyn A Sun; Gizem A Gökalp; Gökhan M Mutlu; Robert B Hamanaka Journal: Am J Respir Cell Mol Biol Date: 2020-11 Impact factor: 6.914
Authors: Jennifer L Larson-Casey; Jessy S Deshane; Alan J Ryan; Victor J Thannickal; A Brent Carter Journal: Immunity Date: 2016-02-23 Impact factor: 31.745
Authors: Ashley R Rackow; David J Nagel; Claire McCarthy; Jennifer Judge; Shannon Lacy; Margaret A T Freeberg; Thomas H Thatcher; R Matthew Kottmann; Patricia J Sime Journal: Eur Respir J Date: 2020-11-26 Impact factor: 16.671