Real-world treatment persistence and predictive factors for discontinuation of antifibrotic therapies in patients with idiopathic pulmonary fibrosis: a post-hoc analysis of two multicenter observational cohort studies in Poland

Abstract

Background: Persistence with antifibrotic medications in patients with idiopathic pulmonary fibrosis (IPF) is crucial for long-term outcomes. However, real-world data regarding treatment persistence patterns in IPF are scarce.

Methods: We conducted a post hoc analysis of two retrospective, real-world, multicenter observational studies (PolExPIR and PolExNIB) that collected clinical data on Polish patients with IPF managed at specialized centers between January 2017 and October 2021. We compared clinical variables between groups of patients who continued and discontinued antifibrotics and evaluated predictive factors for treatment discontinuation.

Results: Overall, 808 patients were included in the analysis. Of these, 278 subjects (34.4%) discontinued therapy over a median follow-up of 16 (8-24) months. The proportion of patients discontinuing therapy was comparable between pirfenidone and nintedanib (37.5% vs. 32.5% respectively; p = 0.15). Additionally, no statistical difference was observed between antifibrotic agents in the distribution of time until treatment discontinuation (log-rank test, p = 0.3). Predictive factors associated with the probability of treatment discontinuation included age (hazard ratio [HR] 1.04; 95% confidence interval [CI] 1.02-1.05), body mass index (BMI, HR 0.97; 95% CI 0.94-0.99), transfer factor of the lung for carbon monoxide (TLco)% predicted (HR 0.98, 95% CI 0.97-0.99), Gender-Age-Physiology (GAP) index score (HR 1.3, 95% CI 1.18-1.42), use of long-term oxygen therapy (LTOT) (HR = 1.7, 95% CI 1.28-2.27) and intermittent dosing adjustment (HR 1.66, 95% CI 1.29-2.15).

Conclusion: In this large population-based cohort of patients with IPF, around one-third discontinued antifibrotics during a study follow-up with no difference in the rates and time to discontinuation between pirfenidone and nintedanib. Clinical predictive factors including age, BMI, TLco% predicted, GAP index score, use of LTOT and intermittent dosing adjustment were associated with the risk of treatment discontinuation.

Keywords: IPF; antifibrotic therapy; idiopathic pulmonary fibrosis; nintedanib; pirfenidone; predictive factors; treatment discontinuation; treatment persistence.

FIGURE 1

Probability of treatment discontinuation in patients starting pirfenidone (blue) and nintedanib (red) over medication exposure period by Kaplan-Meier analysis (shadow lines are reflecting 95% confidence interval).

FIGURE 2

(A–E) presenting the difference in clinical variables in patients with IPF according to drug persistence status: (A) The difference in age of patients with IPF according to drug persistence status. (B) The difference in TLco% predicted of patients with IPF according to drug persistence status. (C) The difference in GAP index score of patients with IPF according to drug persistence status. (D) The difference in the use of LTOT in patients with IPF according to drug persistence status. (E) The difference in the IDA in patients with IPF according to drug persistence status. Abbreviations: IPF, idiopathic pulmonary fibrosis; TL_CO, transfer factor of the lung for carbon monoxide; GAP index, gender, age, and two physiology variables (FVC and TL_CO); LTOT, long-term oxygen therapy; IDA, intermittent dosing adjustment. Boxes represent medians and interquartile ranges, while whiskers represent the 5th and 95th percentiles.

FIGURE 3

Forest plot showing hazard ratios and 95% confidence intervals obtained by univariable Cox proportional hazards regression models of independent clinical variables associated with antifibrotic treatment discontinuation. Abbreviations: BMI, body mass index; GAP index, gender, age, and two physiology variables (FVC and TL_CO); FVC%, forced vital capacity % predicted; TL_CO%, transfer factor of the lung for carbon monoxide % predicted; LTOT, long-term oxygen therapy.

FIGURE 4

Forest plot showing hazard ratios and 95% confidence intervals obtained by multivariable Cox proportional hazards regression model of independent clinical variables associated with antifibrotic treatment discontinuation. Abbreviations: BMI, body mass index; GAP index, gender, age, and two physiology variables (FVC and TL_CO); FVC%, forced vital capacity % predicted; TL_CO%, transfer factor of the lung for carbon monoxide % predicted; LTOT, long-term oxygen therapy.