Impact of reduction in antifibrotic treatment on mortality in idiopathic pulmonary fibrosis

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Introduction: Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease for which two effective antifibrotics, nintedanib and pirfenidone, are available. However, many patients receive a reduced dosage or pause treatment due to side effects although the impact of antifibrotic treatment reduction is uncertain. Methods: We retrospectively investigated the impact of antifibrotic treatment reduction on death in a large real-life IPF cohort. The primary endpoint of the analyses was time until death by any cause. Five patient groups were defined based on treatment intensity (full, reduced or no treatment) and the antifibrotic drug type (pirfenidone or nintedanib). Between group survival was compared using Cox proportional hazards analysis adjusted for age, sex, smoking status, and lung function at baseline. Results: 375 patients from the Danish PFBIO-cohort were followed from April 2016 until November 2021 with a median follow-up time of 1.84 years. Of patients receiving nintedanib and pirfenidone, 80.19% and 67.42% had reduced treatment, respectively, when considering the entire follow-up period. Treatment with nintedanib and pirfenidone was associated with improved survival compared to no antifibrotic treatment independent of treatment intensity (nintedanib: HR: 0.31, 95%-CI: 0.19–0.53, p < 0.001 & pirfenidone: HR: 0.26, 95%-CI: 0.16–0.42, p < 0.001). Nintedanib and pirfenidone in lower intensities were not associated with worse survival outcomes. Conclusion: A substantial proportion of patients with IPF receive reduced antifibrotic treatment to ameliorate the side effects associated with a full dosage regime. Treatment with nintedanib and pirfenidone, independent of treatment intensity, was preferable over no antifibrotic treatment in improving survival and reduced dose appears to be a good alternative if full dose is not tolerated.

OriginalsprogEngelsk
Artikelnummer107015
TidsskriftRespiratory Medicine
Vol/bind204
ISSN0954-6111
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
This work was funded by unrestricted research grants from Aase og Ejnar Danielsens Fond ( Aase and Einar Danielsens Foundation ), Roche a/s and Skibsreder Per Henriksen , R og Hustrus Fond ( Shipowner Per Henriksen , R and wife Foundation ). The funding sources had no influence on the study design; the collection, analysis, or interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication.

Funding Information:
This work was funded by unrestricted research grants from Aase og Ejnar Danielsens Fond (Aase and Einar Danielsens Foundation), Roche a/s and Skibsreder Per Henriksen, R og Hustrus Fond (Shipowner Per Henriksen, R and wife Foundation). The funding sources had no influence on the study design; the collection, analysis, or interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication.SP reports unrestricted research grants from Aase og Ejnar Danielsens Fond, Roche and Skibsreder Per Henriksen, R. og Hustrus Fond.NH reports unrestricted research grants from Aase og Ejnar Danielsens Fond, Roche and Skibsreder Per Henriksen, R. og Hustrus Fond.SBS reports participation in advisory board meetings for Boehringer Ingelheim and Roche, receiving support for participation in scientific meetings from Boehringer Ingelheim and lecture fees from Boehringer Ingelheim and Astra Zeneca …

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