Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial

• Published in: The Lancet (British edition) 2009-07, Vol.374 (9685), p.222-228
• Main Authors: King, Talmadge E, Prof, Albera, Carlo, MD, Bradford, Williamson Z, MD, Costabel, Ulrich, Prof, Hormel, Phil, MS, Lancaster, Lisa, MD, Noble, Paul W, Prof, Sahn, Steven A, Prof, Szwarcberg, Javier, MD, Thomeer, Michiel, MD, Valeyre, Dominique, MD, du Bois, Roland M, Prof
• Format: Article
• Language: English
• Subjects: Aged; Analysis of Variance; Biological and medical sciences; Carbon monoxide; Clinical outcomes; Clinical trials; Design; Disease Progression; Double-Blind Method; Drug Administration Schedule; Drugs; Europe - epidemiology; Exercise Test; Female; General aspects; Humans; Idiopathic Pulmonary Fibrosis - diagnosis; Idiopathic Pulmonary Fibrosis - drug therapy; Idiopathic Pulmonary Fibrosis - mortality; Injections, Subcutaneous; Interferon; Interferon-gamma - adverse effects; Interferon-gamma - therapeutic use; Internal Medicine; Kaplan-Meier Estimate; Lung diseases; Lungs; Male; Medical sciences; Mortality; North America - epidemiology; Pneumology; Proportional Hazards Models; Pulmonary Diffusing Capacity; Recombinant Proteins; Respiratory function; Respiratory system : syndromes and miscellaneous diseases; Severity of Illness Index; Survival; Survival Rate; Treatment Failure; Vital Capacity
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(09)60551-1

Summary 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 μg 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. Findings 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. Interpretation 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. Funding InterMune.