Unbound MEDLINE

Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis.

Abstract

BACKGROUND
A combination of prednisone, azathioprine, and N-acetylcysteine (NAC) has been widely used as a treatment for idiopathic pulmonary fibrosis. The safety and efficacy of this three-drug regimen is unknown.
METHODS
In this randomized, double-blind, placebo-controlled trial, we assigned patients with idiopathic pulmonary fibrosis who had mild-to-moderate lung-function impairment to one of three groups -- receiving a combination of prednisone, azathioprine, and NAC (combination therapy), NAC alone, or placebo -- in a 1:1:1 ratio. The primary outcome was the change in longitudinal measurements of forced vital capacity during a 60-week treatment period.
RESULTS
When approximately 50% of data had been collected (with 77 patients in the combination-therapy group and 78 in the placebo group), a planned interim analysis revealed that patients in the combination-therapy group, as compared with the placebo group, had an increased rate of death (8 vs. 1, P=0.01) and hospitalization (23 vs. 7, P<0.001). These observations, coupled with no evidence of physiological or clinical benefit for combination therapy, prompted the independent data and safety monitoring board to recommend termination of the combination-therapy group at a mean follow-up of 32 weeks. Data from the ongoing comparison of the NAC-only group and the placebo group are not reported here.
CONCLUSIONS
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. (Funded by the National Heart, Lung, and Blood Institute and the Cowlin Family Fund; ClinicalTrials.gov number, NCT00650091.).

Links

  • Publisher Full Text
  • Authors

    Idiopathic Pulmonary Fibrosis Clinical Research Network, Raghu G, Anstrom KJ, King TE, Lasky JA, Martinez FJ

    Source

    The New England journal of medicine 366:21 2012 May 24 pg 1968-77

    MeSH

    Acetylcysteine
    Aged
    Azathioprine
    Disease Progression
    Double-Blind Method
    Drug Therapy, Combination
    Female
    Hospitalization
    Humans
    Kaplan-Meier Estimate
    Male
    Medication Adherence
    Middle Aged
    Prednisone
    Pulmonary Fibrosis
    Treatment Outcome
    Vital Capacity

    Pub Type(s)

    Comparative Study
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22607134