Impact of Antifibrotic Adherence and Dosing on Risk of Mortality and Hospitalization in Idiopathic Pulmonary Fibrosis: A Nested Case-Control Study.

Abstract

Antifibrotics including nintedanib and pirfenidone are effective in slowing the decline of lung function for patients with idiopathic pulmonary fibrosis (IPF). However, their adoption rates are remarkably low, and substantial proportions of patients undergo dose reduction or treatment discontinuation because of the high incidence of adverse events. What is the impact of treatment modification on all-cause mortality and hospitalization? Using a large administrative database, we identified patients with IPF who initiated antifibrotics. A nested case-control design was used to match cases and controls at a 1:1 ratio and conditional logistic regression was performed to estimate the effect of antifibrotic adherence and dosing. Adherence was measured using the proportion of days covered (PDC). Both adherence and dosing were determined based on the exposure period between antifibrotic initiation (cohort entry date) and outcome occurrence (index date). Adherence (PDC ≥ 0.75) was associated with lower risk of mortality (OR=0.563, p<0.001), regardless of which antifibrotic was used. Patients on reduced dose had a significantly greater risk of mortality compared to those on standard dose (OR=1.57, p=0.024), but this was only seen in those who started nintedanib. For hospitalization, adherence was associated with a lower risk (OR=0.692, p=0.016) overall, and reduced doses were associated with a higher risk (OR=1.667, p=0.008) only among patients who started nintedanib. Among patients who started pirfenidone, neither adherence nor dose was associated with the risk of hospitalization. Results of this study suggest that antifibrotic adherence and dosing are important factors that influence mortality and hospitalization. A multidisciplinary approach involving nutritionists, drug clinical educators, and other key stakeholders to facilitate early access, affordable treatment, and adverse event mitigation may enhance adherence and ultimately improve patient outcomes.