Effectiveness of pirfenidone in elderly patients with advanced functional impairment: a real-world study in idiopathic pulmonary fibrosis

<bold>Background:</bold> Clinical trials for the approval of pirfenidone in idiopathic pulmonary fibrosis (IPF) included patients with age ≤ 80 years, FVC ≥ 50%pred and DLCO ≥ 35%pred. Effectiveness in patients who progress beyond these criteria is not yet fully investigated. <bold>Aim of the study:</bold> To evaluate the effectiveness of pirfenidone in patients who, during follow-up, progress beyond the criteria adopted in clinical trials. <bold>Methods:</bold> This is a single-center retrospective observational study of patients with IPF treated in label with pirfenidone from December 2011 to October 2023. We compared the monthly decline in FVC and DLCO%pred before and after the progression beyond one or more of the criteria adopted in clinical trials. <bold>Results:</bold> 175 patients were included in the study, with a mean follow-up of 39.1 months (SD 29.5 months). Seventy-six of them remained within all criteria (control group), 73 passed one criterion, 25 two criteria and 1 all criteria. There was no difference in the monthly decline of the control group and the others who overcame one or two criteria, either in FVC (median -7.7, -8.5, and -7 ml/month, respectively) or in DLCO%pred (median −0.1, −0.2, and −0.4%/month, respectively). Considering individual patients, their monthly decline was similar before and after progressing beyond a criterion. However, a trend towards an accelerated FVC decline emerged when all patients who passed one of the criteria were analyzed together (mean -6.7 ml/month before vs -12 ml/month after passing a criterion, p=0.065). <bold>Conclusions:</bold> The effectiveness of pirfenidone appeared to be maintained even in elderly patients with advanced functional impairment.