Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial.
BACKGROUND
An efficacious medical therapy for idiopathic pulmonary fibrosis (IPF) remains elusive.


OBJECTIVE
To explore the efficacy and safety of etanercept in the treatment of IPF.


METHODS
This was a randomized, prospective, double-blind, placebo-controlled, multicenter exploratory trial in subjects with clinically progressive IPF. Primary endpoints included changes in the percentage of predicted FVC and lung diffusing capacity for carbon monoxide corrected for hemoglobin (Dl(CO(Hb))) and change in the alveolar to arterial oxygen pressure difference P(a-a)(O(2)) at rest from baseline over 48 weeks.


RESULTS
Eighty-eight subjects received subcutaneous etanercept (25 mg) or placebo twice weekly as their sole treatment for IPF. No differences in baseline demographics and disease status were detected between treatment groups; the mean time from first diagnosis was 13.6 months and mean FVC was 63.9% of predicted. At 48 weeks, no significant differences in efficacy endpoints were observed between the groups. A nonsignificant reduction in disease progression was seen in several physiologic, functional, and quality-of-life endpoints among subjects receiving etanercept. There was no difference in adverse events between treatment groups.


CONCLUSIONS
In this exploratory study in patients with clinically progressive IPF, etanercept was well tolerated. Although there were no differences in the predefined endpoints, a decreased rate of disease progression was observed on several measures. Further evaluation of TNF antagonists in the treatment of IPF may be warranted. Clinical trial registered with www.clinicaltrials.gov (NCT 00063869).
Raghu
Ganesh
G
Division of Pulmonary and Critical Care Medicine, Campus Box 356175, University of Washington, Seattle, WA 98195-6522, USA. graghu@u.washington.edu
Brown
Kevin K
KK
Costabel
Ulrich
U
Cottin
Vincent
V
du Bois
Roland M
RM
Lasky
Joseph A
JA
Thomeer
Michiel
M
Utz
James P
JP
Khandker
Rezaul K
RK
McDermott
Lawrence
L
Fatenejad
Saeed
S
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D002248:Carbon Monoxide / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000097:blood; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011658:Pulmonary Fibrosis / Q000188:drug therapy*; D011788:Quality of Life; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012107:Research Design; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D002248:Carbon Monoxide; D000068800:Etanercept; D010100:Oxygen