Prevalence and predictors of response to long-term treatment in patients with idiopathic pulmonary fibrosis (IPF).

<bold>Background</bold>. The natural history of IPF remains unpredictable despite antifibrotic treatment. In addition, some patients stop treatment due to adverse events. To date, no data exists on either the effect of long-term treatment or predictors of treatment response. <bold>Aim</bold>. To evaluate the functional trajectory of IPF patients treated with antifibrotics (nintedanib or pirfenidone) for at least 3 years and to establish predictors of treatment response. <bold>Methods.</bold> This multicenter study enrolled IPF patients provided they had stopped treatment for no longer than a month during the three-year study period (Jan. 2014-Dec. 2023). Based on the absolute decline of FVC%predicted (pred.) observed during the 3-year treatment and normalized per year, patients were defined as progressors (≥5%) or non-progressors (<5%). <bold>Results.</bold>144 patients were included in the analysis. 37/144(26%) patients progressed while on treatment. Progressors were more likely to be non-smokers compared to non-progressors (43%vs.21,p=0.006), with higher occurrence of diarrhea (51%vs.33,p=0.04), a higher FVC%pred. at diagnosis [median 93%(54-149) vs. 83(53-124);p=0.03] and with a higher FVC%pred. decline in the first-year of follow-up (8%vs. 0,p<0.0001). FVC%pred. at diagnosis, FVC%pred. in the first-year decline, being non-smokers and complaining of diarrhea were independent predictors of progression. <bold>Conclusion.</bold> About one quarter of IPF patients experience functional progression despite complete adherence to antifibrotic therapy. Better preserved lung function at diagnosis, functional decline in the first year of treatment, occurrence of diarrhea and non-smoking status were independent predictors of disease progression.