Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial.
BACKGROUND
Idiopathic pulmonary fibrosis is a fatal disease for which no effective treatment exists. We assessed whether treatment with interferon gamma-1b improved survival compared with placebo in patients with idiopathic pulmonary fibrosis and mild-to-moderate impairment of pulmonary function.


METHODS
826 patients with idiopathic pulmonary fibrosis were enrolled from 81 centres in seven European countries, the USA, and Canada. Patients were randomly assigned (double-blind) in a 2:1 ratio to receive 200 microg interferon gamma-1b (n=551) or equivalent placebo (n=275) subcutaneously, three times per week. Eligible patients were aged 40-79 years, had been diagnosed in the past 48 months, had a forced vital capacity of 55-90% of the predicted value, and a haemoglobin-corrected carbon monoxide diffusing capacity of 35-90% of the predicted value. The primary endpoint was overall survival time from randomisation measured at the second interim analysis, when the proportion of deaths had reached 75% of those expected by the study conclusion. This study is registered with ClinicalTrials.gov, number NCT00075998.


RESULTS
At the second interim analysis, the hazard ratio for mortality in patients on interferon gamma-1b showed absence of minimum benefit compared with placebo (1.15, 95% CI 0.77-1.71, p=0.497), and indicated that the study should be stopped. After a median duration of 64 weeks (IQR 41-84) on treatment, 80 (15%) patients on interferon gamma-1b and 35 (13%) on placebo had died. Almost all patients reported at least one adverse event, and more patients on interferon gamma-1b group had constitutional signs and symptoms (influenza-like illness, fatigue, fever, and chills) than did those on placebo. Occurrence of serious adverse events (eg, pneumonia, respiratory failure) was similar for both treatment groups. Treatment adherence was good and few patients discontinued treatment prematurely in either group.


CONCLUSIONS
We cannot recommend treatment with interferon gamma-1b since the drug did not improve survival for patients with idiopathic pulmonary fibrosis, which refutes previous findings from subgroup analyses of survival in studies of patients with mild-to-moderate physiological impairment of pulmonary function.


BACKGROUND
InterMune.
King
Talmadge E
TE
Department of Medicine, University of California San Francisco, San Francisco, CA 94143-0120, USA. tking@medicine.ucsf.edu
Albera
Carlo
C
Bradford
Williamson Z
WZ
Costabel
Ulrich
U
Hormel
Phil
P
Lancaster
Lisa
L
Noble
Paul W
PW
Sahn
Steven A
SA
Szwarcberg
Javier
J
Thomeer
Michiel
M
Valeyre
Dominique
D
du Bois
Roland M
RM
D000368:Aged; D000704:Analysis of Variance; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005060:Europe / Q000453:epidemiology; D005080:Exercise Test; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000009:adverse effects / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D009656:North America / Q000453:epidemiology; D016016:Proportional Hazards Models; D011653:Pulmonary Diffusing Capacity; D011994:Recombinant Proteins; D012720:Severity of Illness Index; D015996:Survival Rate; D017211:Treatment Failure; D014797:Vital Capacity
D011994:Recombinant Proteins; D007371:Interferon-gamma