Yet H. Khor, Max Schulte, Kerri A. Johannson, Veronica Marcoux, Jolene H. Fisher, Deborah Assayag, Helene Manganas, Nasreen Khalil, Martin Kolb, Christopher J Ryerson for the Austin ILD Registry and CARE-PF Investigators
European Respiratory Journal 2023; DOI: 10.1183/13993003.02163-2022

Abstract

Background Little is known about generalisability of randomised controlled trials (RCTs) for idiopathic pulmonary fibrosis (IPF). We evaluated eligibility criteria for phase III IPF RCTs to determine their representativeness in clinical registries, and calculated forced vital capacity (FVC) changes according to eligibility criteria.

Methods Common eligibility criteria used in >60% of IPF RCTs were identified from a literature search and applied to patients with IPF from prospective Australian and Canadian registries. Additional pre-specified criteria of 6-min walk distance (6 MWD) and different measures of preceding disease progression were also evaluated. Joint longitudinal-survival modelling was used to compare FVC decline according to eligibility for individual and composite criteria.

Results Of 990 patients with IPF, 527 (53%) met all common RCT eligibility criteria at the first clinic visit, including 343 with definite IPF and 184 with radiological probable usual interstitial pneumonia pattern without histological confirmation (i.e., provisional IPF). The percentages of eligible patients for landmark RCTs of nintedanib and pirfenidone were 19–50%. Adding 6 MWD ≥150 m and different measures of preceding disease progression to the composite common criteria reduced the percentages of patients meeting eligibility to 52% (n=516) and 4–18% (n=12–61), respectively. Patients meeting the composite common criteria had less rapid 1-year FVC decline than those who did not (−90 versus −103 ml, p=0.01). Definite IPF generally had more rapid 1-year FVC decline compared to provisional IPF.

Conclusions Eligibility criteria of previous IPF RCTs have limited generalisability to clinical IPF populations, with FVC decline differing between eligible and ineligible populations.