Idiopathic pulmonary fibrosis is the most common and deadly of the “idiopathic” interstitial lung diseases. It is estimated that in the UK alone, IPF is responsible for 5,000 deaths per year, with a mortality rate greater than that of many common cancers (1). Despite a median survival of only 3 years from diagnosis, there is a wide variability in disease course in IPF (2). Some patients will have relatively prolonged periods of stability or only a gradual progression of disease, whereas others will have extremely rapid disease progression, leading to death in less than a year, and others still will experience acute exacerbations, periods of catastrophic worsening in their lung disease over only a few weeks, whose frequency increases with worsening disease severity.
Over the past decade, there have been a number of trials yielding negative or uncertain results, such that, until recently, IPF was an untreatable disease. The recent results of phase 3 trials on two anti-fibrotic drugs, pirfenidone and Nintedanib, respectively (3,4), have represented a major breakthrough for patients with IPF. They show that treatment with pirfenidone or nintedanib is associated with a reduction in FVC decline by roughly 50%, and the FDA has approved the use of both in IPF. The magnitude of effect is remarkably similar b etween the two drugs. However, neither halts disease progression, and ultimately the only treatment unequivocally linked to improved survival remains lung transplant. A number of targets are being investigated in ongoing trials, and there is now the challenge of future design of drug trials. The new drugs will be compared with pirfenidone or Nintedanib, but this will mean smaller longitudinal reductions in FVC, the currently most used primary endopoint. Combined endpoints are likely to be needed to increase the power of future trials in IPF…..