Assessing the treatment effect from multiple trials in idiopathic pulmonary fibrosis

Abstract

The magnitude of treatment effect can be assessed by a number of methods. One method of collectively analysing data is that used by the Cochrane Collaboration. Their systematic reviews identify, analyse and present research-based evidence in an accessible format. These reviews may contain meta-analyses combining data from multiple studies to provide robust evaluations of overall treatment effects. In 2003, Cochrane reviews of data for treatment with corticosteroids in idiopathic pulmonary fibrosis (IPF) found no evidence supporting their use; similarly, reviews of immunomodulatory agents found very little evidence to support their use. A recent update of these Cochrane reviews failed to identify any evidence supporting the use of corticosteroids in IPF; however, a review of non-steroid agents in the treatment of IPF identified 15 clinical trials suitable for analysis. Two trials of interferon-γ-1b were combined, and no treatment effect was observed in terms of survival. Two Japanese trials of treatment with pirfenidone were combined, and a positive effect of pirfenidone on pulmonary function decline was observed. Meta-analysis of three phase III studies suggested that pirfenidone significantly increased progression-free survival by 30%. The findings of this systematic review, although not presenting new original data, together with an acceptable safety profile, suggest that pirfenidone may have a role in IPF treatment.

Figure 1.

Effects of oral β-blockers for a secondary prevention of mortality in patients surviving a myocardial infarction Individual randomised clinical trials and overall meta-analysis result. z=-4.47, p<0.00001. Reproduced from [5] with permission from the publisher.

Figure 2.

Two systematic searches for randomised clinical trials of non-steroid agents in idiopathic pulmonary fibrosis (IPF) up to 2003 and up to 2010. IFN: interferon.

Figure 3.

Randomised clinical trials of non-steroid agents in idiopathic pulmonary fibrosis eligible for meta-analyses. IFN: interferon.

Figure 4.

Meta-analysis of overall survival in idiopathic pulmonary fibrosis with interferon (IFN)-γ-1b. HR: hazard ratio; df: degree of freedom. Reproduced from [14] with permission from the publisher.

Figure 5.

Meta-analysis of absolute change in vital capacity for pirfenidone in idiopathic pulmonary fibrosis. Reproduced from [14] with permission from the publisher.

Figure 6.

Meta-analysis of progression-free survival with pirfenidone in idiopathic pulmonary fibrosis. Reproduced with modificaton from [14] with permission from the publisher.