Eligibility for anti‐fibrotic treatment in idiopathic pulmonary fibrosis depends on the predictive equation used for pulmonary function testing

Abstract

Background and objective Publicly funded therapy for idiopathic pulmonary fibrosis (IPF) relies on percentage predicted values from pulmonary function testing, for example Australian patients must have a forced vital capacity ≥50% (%FVC), transfer factor of the lung for carbon monoxide ≥ 30% (%TLco) and forced expiratory volume in 1 s (FEV1)/FVC ratio > 0.7. Despite defined cut‐off values, no jurisdiction prescribes a reference equation for use; multiple equations exist. We hypothesized that access to subsidized treatment varies depending on the chosen equation. The %FVC and %TLco from different commonly used reference equations across general respiratory patients, and IPF‐specific patients, were compared. Methods FVC and TLco measurements from a large general respiratory laboratory and the Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR) database were analysed using multiple equations. Differences between %FVC and %TLco for each equation were calculated, with particular interest in classification of patients (%) at the threshold for subsidized treatment. Results A total of 20 378 general respiratory database results were analysed. The %FVC ≥ 50% increased from 86% with the Roca equation to 96% with Quanjer (European Coal and Steal Community, ECSC) and %TLco≥30% increased from 91% with Paoletti to 98% with Thompson. However, overall increase in eligibility for subsidized treatment was modest, varying from 48.2% to 49.2%. A total of 545 AIPFR database results were analysed. The %FVC ≥ 50% increased from 73% with Roca to 94% with Quanjer (ECSC) and %TLco≥30% increased from 87% with Paoletti to 96% with Miller. Overall eligibility for subsidized treatment in the AIPFR group varied from 73.6% to 82.8% between surveyed interstitial lung disease (ILD) centres based entirely on the equation used. Conclusion Substantial variability exists between reference equations, impacting access to subsidized treatment. Treating clinicians should be aware of this when assessing patients around public funding thresholds.

Antifibrotic Drug Use in Patients with Idiopathic Pulmonary Fibrosis. Data from the IPF-PRO Registry

“…Because the registry is conducted in a real-world setting, there was a degree of missing data and variability in follow-up time. Only one equation for calculation of FVC% predicted and one equation for calculation of D l CO % predicted were used, and different reference equations may have provided different results for the proportions of patients in the registry who met inclusion criteria for the INPULSIS and ASCEND trials based on the cutoffs for FVC and D l CO ( 36 , 37 ).…”

Official ERS technical standard: Global Lung Function Initiative reference values for static lung volumes in individuals of European ancestry

“…Changing from currently utilised reference ranges (for example ECSC) to the GLI reference range will probably lead to differences in the proportion of patients classified as having abnormal lung function. Studies of this issue have been reported for spirometry [37,38] and the single-breath gas transfer test [39][40][41] and all have broadly noted that the impact of changing to GLI equations for these tests varies with age and sex and can impact on the potential eligibility for treatments [42]. Studies assessing the impact of switching to the GLI lung volume equations will be required to help inform health professionals and their patients.…”

Putting lung function reference equations into context

“…Approximately 34 out of 98 patients (total n=528) who were ineligible for treatment using the European Community for Steel and Coal reference set [ 6 ] to calculate FVC % predicted became eligible when using the Third National Health and Nutrition Examination Survery spirometry reference set [ 7 ], and 25 became eligible using the GLI 2012 reference set [ 2 ] instead. The second study from Australia, where antifibrotic lung function eligibility criteria is FVC ≥50% predicted and T LCO ≥30% predicted, found variation in eligibility ranged from 74% to 86% dependent on the reference sets chosen [ 8 ]. Table 3 shows the variation in FVC % predicted and T LCO % predicted in a selection of commonly used reference sets using the presented case's gender, age and height.…”