The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, has stopped one arm of a three arm multi-centre, clinical trial studying treatments for the lung-scarring disease idiopathic pulmonary fibrosis (IPF) for safety concerns.
The NHLBI statement can be found at: http://www.nih.gov/news/health/oct2011/nhlbi-21.htm
The trial found that people with IPF receiving a currently used ‘triple-drug’ therapy consisting of prednisolone*, azathioprine, and N-acetylcysteine (NAC) had worse outcomes than those who received placebos or inactive substances. The study is continuing with the remaining 2 –arms; N-acteylcysteine versus placebo arms. Definitive statements on the true significance of these data cannot be made until further analyses are available. The outcomes described in the interim analysis are unexpected (atypical) and suggest there may be important differences between both the phenotype and management of IPF subjects enrolled in the study and IPF patients seen in clinical practice. However the BTS is able to give some guidance on the use of prednisolone, azathioprine and NAC based on these interim data:
1.The BTS ILD SAG recommends that new patients with definite IPF should NOT be initiated on a regimen containing prednisolone plus azathioprine
2. No concerns have been raised as a result of preliminary analysis of the n-acetylcysteine monotherapy arm of the study. The preliminary announcement by the NHLBI has no immediate implications on the use of NAC in IPF
3. ‘In patients with definite IPF already receiving combination prednisolone/azathioprine/n-acetylcysteine therapy, it is recommended that azathioprine therapy in particular should be withdrawn if there is evidence of disease progression (declining lung function). In patients established on triple therapy with ‘stable’ disease, the decision to withdraw should be on a cases-by-case basis, but the threshold for withdrawing azathioprine from elderly patients should be low.
4. Patients with fibrotic ILD that is not definite IPF (e.g, NSIP, HP) should continue to be managed according to clinical judgement and the BTS ILD Guidelines.
*Please note that US trial used prednisone. The BTS ILD Guidelines refer to prednisolone.