Interstitial lung disease · Immunosuppression in IPF
Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis
| Design | Randomised, double-blind, placebo-controlled trial, arm terminated early on safety grounds |
|---|---|
| Treatment | Combination prednisone, azathioprine and N-acetylcysteine |
| Control | Placebo |
| Population | 155 patients with idiopathic pulmonary fibrosis at the interim analysis: 77 combination therapy and 78 placebo |
| Follow-up | 60 weeks planned |
| Primary endpoint | Change in forced vital capacity |
| Result | At the planned interim analysis, with about 50% of data collected, the combination group had more deaths (8 versus 1, p=0.01) and more hospitalisations (23 versus 7, p<0.001), with no evidence of physiological or clinical benefit. The data and safety monitoring board recommended terminating the combination arm. |
| Secondary endpoints | Death, hospitalisation, acute exacerbation, adverse events |
Increased risks of death and hospitalization were observed in patients with idiopathic pulmonary fibrosis who were treated with a combination of prednisone, azathioprine, and NAC, as compared with placebo. These findings provide evidence against the use of this combination in such patients.
The trial authors, in the published abstract
For decades this combination was recommended therapy for IPF on pathophysiological reasoning about inflammation. Eight deaths against one, at the halfway point. It is the single most important negative trial in interstitial lung disease, and it cleared the ground for the antifibrotic era of ASCEND and INPULSIS two years later. Note that immunosuppression is not universally wrong in ILD — EVER-ILD shows it helps in inflammatory NSIP. It is wrong in IPF.
Raghu G, Anstrom KJ, King TE Jr, et al. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med 2012 May 24;366(21):1968-77.