LAUSR

Interstitial lung diseases (ILD) encompass a heterogeneous group of inflammatory and fibro-proliferative disorders of varying aetiologies. Amongst these, idiopathic pulmonary fibrosis (IPF) is the most studied and archetypal fibrosing ILD. It is now recognized that a significant proportion of patients with other fibrosing ILD manifest a progressive phenotype, commonly termed as progressive fibrosing ILD (PF-ILD), with a similar disease course and underlying pathophysiology to IPF. The emergence of antifibrotic therapies has transformed the landscape of IPF management, with established efficacy in slowing disease progression, reducing acute exacerbation rates and improving survival. Similar therapeutic benefits have been shown in recent clinical trials of antifibrotic therapies in PF-ILD populations. While there is increasing clinical and research interest in PFILD, many questions remain unanswered. Using a prospective ILD registry of 346 well-characterized patients with multidisciplinary diagnosis, we explored the patient characteristics and potential healthcare implications of extending antifibrotic therapies to the PF-ILD cohort. The diagnostic criteria of PF-ILD are yet to be formalized; commonly proposed criteria include a combination of physiological, clinical and imaging progression over a 2-year period. In the INBUILD trial, the progressive phenotype was defined as: a relative forced vital capacity (FVC) decline ≥10% predicted or a combination of ≥2 of the following criteria: a relative FVC decline of 5–10% predicted, progressive symptoms or imaging changes. Of the 118 patients with non-IPF fibrosing ILD in our registry, 47.5% (n = 56) met the INBUILD trial criteria of progressive phenotype within 2-year intervals during a median follow-up of 4.3 (interquartile range 3.1–7.7) years. Most patients exhibited progression as a relative decline in FVC ≥10% predicted (n = 53). The most common diagnoses of this PF-ILD cohort were unclassifiable ILD (n = 16), hypersensitivity pneumonitis (n = 14) and connective tissue disease-associated ILD (n = 12). Time from diagnosis to progression was highly variable in our cohort (Fig. 1), with median duration of 2.24 (interquartile range 0.99–3.25) years. Contrary to previously reported physician expectations of the development of a progressive phenotype occurring 11–15 months following the diagnosis, more than 20% of patients demonstrated progression after 4 years from diagnosis. Given our data set was retrospectively analysed, there were variations in the frequency of follow-up which may have implications for when and how frequently the progressive phenotype was recognized. Nevertheless, our findings are reflective of contemporary clinical practice at a quaternary institution. Hence, longitudinal follow-up with serial assessment in non-IPF fibrosing ILD patients is warranted, including in those who may initially appear to have stable disease. The majority of PF-ILD patients (n = 43; 76.8%) in our cohort had received immunosuppressive therapy consisting of prednisolone, mycophenolate, methotrexate and azathioprine, either alone or in combination. This highlights the urgent need for alternate treatments in this population to address the deficiencies in existing therapeutic approaches. While increasing age is a major risk factor for IPF, non-IPF ILD can affect patients across all ages. We hypothesize that the PF-ILD population will be younger than that seen in IPF. Concordantly, our PF-ILD group had a significantly lower mean age of onset than the IPF group (67.4 8.8 vs 75.3 8.1 years; P < 0.01). Given this younger age of the PF-ILD population and the resultant risks of cumulative impairment over a prolonged period of time, the importance of slowing or halting disease progression is heightened in these patients. With the inflammatory pathogenic basis of many PF-ILD, concurrent use of antifibrotic and immunosuppressive therapy could be considered but would need to be weighed up against the potential higher rates of drug-related adverse effects, and requires further exploration. While there is currently minimal realworld experience on the utilization of antifibrotic therapies in PF-ILD, our local experience with IPF suggests