A real world retrospective observational study exploring the effectiveness and safety of antifibrotics in idiopathic pulmonary fibrosis

Abstract

Background Pirfenidone and nintedanib are the only disease-modifying treatments available for idiopathic pulmonary fibrosis (IPF). Our aim was to test their effectiveness and safety in clinical practice.Methods This is a single centre retrospective observational study undertaken at a specialised interstitial lung disease centre in England. Data including progression-free survival (PFS), mortality and drug tolerability were compared between IPF patients on antifibrotic therapies and an untreated control group who had a forced vital capacity percentage (FVC %) predicted within the licensed antifibrotic treatment range.Results 104 patients received antifibrotic therapies and 64 control patients were identified. PFS at 6 months was significantly greater in the antifibrotic group (75.0%) compared to the control group (56.3%) (p=0.012). PFS was not significant at 12 or 18 months. The 12-month post-treatment mean decline in FVC% predicted (-4.6±6.2%) was significantly less than the 12-month pre-treatment decline (-10.4 ±11.8%) (p=0.039). The 12-month mortality rate was not significantly different between the antifibrotic group (25.3%) and the control group (35.5%) (p=0.132). Baseline BMI≤25, baseline DLco% predicted ≤35 and antifibrotic discontinuation within 3 months were independent predictors of 12-month mortality. Antifibrotic discontinuation was significantly higher by 3 and 6 months for patients on pirfenidone than those on nintedanib (p=0.006 and p=0.044, respectively). Discontinuation at 12 months was not significantly different (p=0.381).Conclusion This real-world study revealed that antifibrotics are having promising effects on PFS, lung function and mortality. These findings may favour commencement of nintedanib as first line antifibrotic therapy, given the lower rates of early treatment discontinuation.

The influence of immortal time bias in observational studies examining associations of antifibrotic therapy with survival in idiopathic pulmonary fibrosis: A simulation study

“…Of the 16 studies reviewed, we found that 14 studies were detected with presence of ITB based on the ITB checklist, while there were insufficient data for assessment of two others. This is consistent with a recently published Letter to Editor (26) that summarized observational studies reporting the effectiveness of antifibrotic therapy on mortality of IPF and identified 14 studies (16-19, 35,41,42,44,45,[53][54][55][56][57] presenting ITB. Compared to a previous study (26), we have included more studies and have provided more detailed information by using the ITB checklist and conducting a simulation study to identify and account for ITB in IPF studies.…”