An article published Online First and in an upcoming edition of The Lancet reports the findings of the INSPIRE trial on treatment of idiopathic pulmonary fibrosis (IPF) with interferon gamma-1b (Ifn-g1b). It is written by Professor Talmadge E King Jr, of the University of California, San Francisco (UCSF), USA and his team. Results show no improvement in survival compared with placebo. There is no effective treatment for IPF which is a fatal disease.

IPF is a disease of unidentified origin. The symptoms are deteriorating shortness of breath, reduced lung volume, and impaired gas exchange in the membranes of the lungs. Outlook is poor and patients usually survive just two to five years after diagnosis. Eventually, it 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. There is evidence from prior studies that Ifn-g1b could be beneficial for IPF patients, mostly those with mild-to-moderate disease. The authors evaluated through a randomized controlled trial whether Ig1b improved survival compared with placebo in IPF patients with mild-to-moderate impairment of lung function.

The researchers assessed 826 patients with IPF from eighty one centers in nine European and North American countries. 551 patients were given 200 µg Ifn-g1b and 275 patients received equivalent placebo subcutaneously, three times per week. The patients were 40 to 79 years and had been diagnosed in the previous two years. Their measures of lung function were: forced vital capacity of 55 to 90 percent of the predicted value, and also reduced carbon monoxide exchanging capacity.

Findings during an interim analysis showed that Ig1b offered no benefit, and as a consequence the study was stopped. After an average period of sixty four weeks, 15 percent of Ifn-1b patients had died versus 13 percent with placebo. More patients in the Ifn-g1b group reported symptoms such as flu-like illness, fatigue, fever and chills than did those in the placebo group. Still, the incidence of serious adverse events was not considerably different between treatment groups.

The authors write in conclusion: “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 a supplementary note, Dr Demosthenes Bouros, of the Democritus University of Thrace, Alexandroupolis, Greece, writes in conclusion: “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.”

“Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial”
Talmadge E King Jr, Carlo Albera, Williamson Z Bradford, Ulrich Costabel, Phil Hormel, Lisa Lancaster, Paul W Noble, Steven A Sahn, Javier Szwarcberg, Michiel Thomeer, Dominique Valeyre, Roland M du Bois, for the INSPIRE Study Group
DOI: 10.1016/S0140-6736(09)60551-1
The Lancet

Written by Stephanie Brunner (B.A.)