Antifibrotic drugs in connective tissue disease-related interstitial lung disease (CTD-ILD): from mechanistic insights to therapeutic applications

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Abstract

Fibrosing interstitial lung disease (ILD) is one of the most important causes of morbidity and mortality in patients with connective tissue diseases (CTDs), which include systemic sclerosis, rheumatoid arthritis, Sjögren’s syndrome, idiopathic inflammatory myositis and systemic lupus erythematosus. The treatment of CTD-ILDs is challenging due to the paucity of proven effective treatments. Recently, two antifibrotic drugs conditionally approved for use in patients with idiopathic pulmonary fibrosis, nintedanib and pirfenidone, have been trialled in CTD-ILDs based on overlapping pathological and clinical features between the two diseases. In this narrative review, we discuss the experimental evidence and clinical trials investigating the efficacy and safety of antifibrotic drugs in patients with CTD-ILDs and the potential mechanisms of action involved. Results from clinical trials suggest that nintedanib use retards lung function decline in progressive fibrotic CTD-ILDs. By contrast, the evidence for the efficacy of pirfenidone in these groups is not equally compelling. Further, well-designed randomized clinical trials are needed to evaluate the efficacy and safety of individual antifibrotic drugs in specific CTD-ILD subgroups.

Keywords: connective tissue diseases, idiopathic inflammatory myopathies, interstitial lung disease, pirfenidone, nintedanib, rheumatoid arthritis, Sjögren’s syndrome, systemic sclerosis.

Citation: Erre GL, Sebastiani M, Manfredi A, Gerratana E, Atzeni F, Passiu G, Mangoni AA. Antifibrotic drugs in connective tissue diseaserelated interstitial lung disease (CTD-ILD): from mechanistic insights to therapeutic applications. Drugs in Context 2020; 9: 2020-8-6. DOI: 10.7573/dic.2020-8-6

Contributions: EGL conceived the study, designed the review methods, searched the databases and drafted and revised the paper. MS conceived the study and critically revised the paper. AM, EG, FA and GP critically revised the paper. AAM conceived the study, searched the databases, drafted and critically revised the paper. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: The authors declare no conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2020/11/dic.2020-8-6-COI.pdf

Acknowledgements: None

Funding declaration: There was no funding associated with the preparation of this article.

Copyright: Copyright © 2020 Erre GL, Sebastiani M, Manfredi A, Gerratana E, Atzeni F, Passiu G, Mangoni AA. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2020 Erre GL, Sebastiani M, Manfredi A, Gerratana E, Atzeni F, Passiu G, Mangoni AA. https://doi.org/10.7573/dic.2020-8-6. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/antifibrotic-drugs-in-connective-tissue-disease-related-interstitial-lung-disease-(ctd-ild):-from-mechanistic-insights-to-therapeutic-applications

Correspondence: Gian Luca Erre, Dipartimento di Scienze Mediche, Chirurgiche e sperimentali, Università degli Studi di Sassari; Dipartimento di Specialità Mediche, Azienda Ospedaliero-Universitaria di Sassari; 07100 Sassari, Italy. glerre@uniss.it

Provenance: Invited; externally peer reviewed.

Submitted: 31 August 2020; Accepted: 13 October 2020; Publication date: 15 January 2021.

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