Idiopathic pulmonary fibrosis (IPF) is a fatal disease for which no effective treatment exists. In this study—the INSPIRE trial—treatment with interferon gamma-1b (Ifn-g1b) is shown not to improve survival compared with placebo. Thus the search for new treatments goes on. The findings are reported in an Article published Online First and in an upcoming edition of The Lancet, written by Professor Talmadge E King Jr, University of California San Francisco (UCSF), USA and colleagues.
IPF is a disease of unknown origin, which is characterised by worsening shortness of breath, reduced lung volume, and impaired gas exchange in the membranes of the lungs. Outlook is poor, with patients typically surviving just 2—5 years from diagnosis. IPF eventually leads to reduced physical abilities and fatigue, which can ultimately end in respiratory failure and death. Ig1b is a purified human protein made from E Coli. Previous studies have suggested a possible benefit for IPF patients given Ifn-g1b, particularly those with mild-to-moderate disease. In this randomised controlled trial, the authors assessed whether Ig1b improved survival compared with placebo in IPF patients with mild-to-moderate impairment of lung function.
The researchers studied 826 patients with IPF from 81 centres in nine European and North American countries. Patients were given 200 µg Ifn-g1b (551 patients) or equivalent placebo (275) subcutaneously, three times per week. Patients were 40—79 years, had been diagnosed in the previous two years, had a forced vital capacity of 55—90% of the predicted value, and also reduced carbon monoxide exchanging capacity (both of these are measures of lung function).
The study was stopped after it was found during an interim analysis that Ig1b offered no benefit. After a median duration of 64 weeks, 15% of Ifn-1b patients had died versus 13% withplacebo. More patients given Ifn-g1b had symptoms such as flu-like illness, fatigue, fever and chills than did those given placebo. However, occurrence of serious adverse events was not significantly different between treatment groups.
The authors conclude: "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."
"The results of our study, the largest randomised controlled clinical trial in patients with idiopathic pulmonary fibrosis, conclusively refute the findings that interferon gamma-1b improves survival. Furthermore, these findings reaffirm the importance of confirming results of subgroup and exploratory analyses in prospective, well designed, randomised placebo-controlled trials."
In an accompanying Comment, Dr Demosthenes Bouros, Democritus University of Thrace, Alexandroupolis, Greece, concludes: "What is clear from INSPIRE is that well-designed and large controlled clinical trials can definitely resolve unanswered questions about the efficacy of novel biological treatments in idiopathic pulmonary fibrosis. Although the negative results of this trial should be regarded as definite, they should not discourage patients to participate in one of the several clinical trials currently underway to find effective treatments for this devastating disease. Suitable patients should be enrolled early in the transplantation list, which is today the only mode of treatment that prolongs survival."
Professor Talmadge E King Jr, University of California San Francisco (UCSF), USA T) +1 415-476-0909 E) tking@medicine.ucsf.edu
Dr Demosthenes Bouros, Democritus University of Thrace, Alexandroupolis, Greece T) +30-25510-76106 /+30-6944757616 E) bouros@med.duth.gr
For full Article and Comment, see: http://press.thelancet.com/ipf.pdf
Journal
The Lancet