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.
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.
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.
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.
InterMune.