Impact of Pirfenidone on Respiratory-related Hospitalizations in Patients with Idiopathic Pulmonary Fibrosis

11 May, 20

Introduction

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease and often results in respiratory related as well as non-respiratory related hospitalizations. Respiratory-related hospitalizations have significant risk of morbidity and mortality and are more frequent than those for acute IPF exacerbations. Pirfenidone is known to reduce the disease progression and decline in exercise capacity. However, the impact of pirfenidone on the risk of respiratory hospitalization and subsequent mortality is not known.

Aim

This study pooled data from three phase III clinical trials and compared the risk of nonelective hospitalization by type (all-cause, respiratory related, and non–respiratory related) and mortality after hospitalization with use of pirfenidone versus placebo over 52 weeks.

Patient Profile

Patients randomized to receive either pirfenidone 2403 mg daily (n=623) or placebo (n=624) in three IPF clinical trials - 2 CAPACITY (Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis) studies and ASCEND (Assessment of Pirfenidone to Confirm the Efficacy and Safety in Idiopathic Pulmonary Fibrosis) were included in the current study .

Method

Study Design

Pooled analysis from 3 phase III randomized placebo-controlled studies of pirfenidone for IPF

Treatment Strategy

Patients were followed for 72-120 weeks and 52 weeks from time of randomization in the CAPACITY and ASCEND trials respectively
The risk of hospitalization over 52 weeks was compared
The risk of death after hospitalization was compared with adjustment for treatment group propensity.

End-points

Risk of nonelective hospitalization by type (all-cause, respiratory related, and non–respiratory related)
Risk of mortality after hospitalization

Results

A total of 1,247 patients (692 from the CAPACITY trials and 555 from the ASCEND trial) were included in the pooled analysis.
A comparison of the risk of hospitalization has been shown in figure 1.

Figure 1. Comparison of risk of hospitalization

The risk of respiratory-related hospitalization was reduced by 48% in patients who received pirfenidone as compared to placebo (7% vs. 12%; hazard ratio [HR], 0.52; p = 0.001)

However, there were no significant differences in all-cause (HR, 0.91; p = 0.528) or non–respiratory-related hospitalization (HR, 1.32; p = 0.145).
Pirfenidone reduced the risk of death after hospitalization up to 52 weeks among the hospitalized patients. Nevertheless, this association was no longer significant with longer follow-up.

Conclusions

Pooled analysis of 3 phase III clinical trials demonstrated that treatment with pirfenidone reduces the risk of respiratory-related hospitalization over the course of 1 year in patients with idiopathic pulmonary fibrosis.
Long-term studies are warranted to evaluate the effect of pirfenidone on hospitalization rates and outcomes of hospitalization.

Am J Respir Crit Care Med. 2017 Sep 15; 196(6): 756–761.