Real World Experience with Pirfenidone on Tolerability and Survival: Indian Study

4 Sep, 20

Introduction

The 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) studies demonstrated improvement in lung function and survival outcomes in patients with idiopathic pulmonary fibrosis (IPF). The survival benefit was associated with a dose of pirfenidone 2400 mg/day. Clinical studies have shown that the full dose of pirfenidone was poorly tolerated by significant proportion of patients and requires dose reduction. Pooled data analyses of CAPACITY and ASCEND studies showed that the reduced doses did not impact the disease progression and mortality at 1 year. In the real-world settings, the discontinuation rates are higher with inconsistent survival outcomes. However, there is lack of prospective real-world data on the efficacy of reduced doses of pirfenidone on survival in IPF.

Study Design

Prospective observational study

Treatment Strategy

Demographics, comorbidities, spirometry findings, diffusion capacity of the lung for carbon monoxide and resting oxygen saturation and 6-min walk distance were recorded.
The cohort was followed up at every 6 months
For survival analysis, the cohort was divided into 2 groups; pirfenidone-group and no-pirfenidone group
The pirfenidone group was divided into full-dose group receiving 2400 mg/day and reduced-dose group receiving <2400 mg/day and compared to no-pirfenidone group
The survival outcomes of full-dose, reduced-dose and no-pirfenidone groups were compared with age, and percentage of predicted forced vital capacity (% predicted FVC) as covariates.

End Points

Maximum tolerated dose of pirfenidone
ADRs
Lung function decline
Predictors of drug discontinuation due to ADRs
Survival outcomes

Results

A total of 128 patients with a mean age of 67.4 years and 77.3% men were recruited
Pirfenidone was initiated in 115 (89.8%)
Full dose and reduced doses were tolerated by 42.6% (n=49) and 44.3% (n=51) respectively
Out of the 22 patients who discontinued the therapy, 15 discontinued due to ADRs
83.5% developed atleast 1 ADR, anorexia, dyspepsia and nausea being the most common
Body mass index (BMI)<20 kg/m² was the only factor that predicted drug discontinuation due to ADRs
There were no significant differences in the median annualized fall in % predicted FVC between the full-dose and reduced-dose groups
The occurrence of acute exacerbation of IPF was not significant between the study groups (p=0.89)
A trend toward significant improvement in survival in those who received full-dose with risk reduction in death by 81% (p=0.045) was observed
Patients in lower dose group also showed improved survival compared to no pirfenidone but differences were not statistically significant
The study groups showed significant improvement in the survival outcomes as compared to no-pirfenidone groups

Conclusions

This is the first study from India which reports that full dose of pirfenidone ie 2400mg/d offers a significant survival advantage in idiopathic pulmonary fibrosis (IPF) patients.

About 42% of the study subjects tolerated the full dose of pirfenidone (2400 mg/day), while 29.6 of the study subjects tolerated a dose of 1800-2400mg/day.