Academic Journal
rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study
| العنوان: | rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study |
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| المؤلفون: | Martina Doubkova, Eva Kriegova, Simona Littnerova, Petra Schneiderova, Martina Sterclova, Vladimir Bartos, Martina Plackova, Monika Zurkova, Radka Bittenglova, Vladimira Lostaková, Lenka Siskova, Pavlina Lisa, Hana Suldova, Michael Doubek, Jana Psikalova, Tomas Snizek, Pavlina Musilova, Martina Vasakova |
| المصدر: | Therapeutic Advances in Respiratory Disease, Vol 15 (2021) |
| بيانات النشر: | SAGE Publishing |
| سنة النشر: | 2021 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Diseases of the respiratory system, RC705-779 |
| الوصف: | Background: The antifibrotic drugs nintedanib and pirfenidone are used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the association of common profibrotic polymorphisms in MUC5B (mucin 5B, rs35705950) and DSP (desmoplakin, rs2076295) on antifibrotic treatment outcomes in IPF. Methods: MUC5B rs35705950 and DSP rs2076295 were assessed in IPF patients ( n = 210, 139 men/71 women) from the Czech EMPIRE registry and age- or sex-matched healthy individuals ( n = 205, 125 men/80 women). Genetic data were collated with overall survival (OS), acute exacerbation episodes, worsening lung function and antifibrotic treatment. Results: We confirmed overexpression of the MUC5B rs35705950*T allele (55.2% versus 20.9%, p < 0.001) and the DSP rs2076295*G allele (80.4% versus 68.3%, p < 0.001) in IPF compared with controls. On antifibrotic drugs, lower mortability was observed in IPF patients with DSP G* allele ( p = 0.016) and MUC5B T* allele ( p = 0.079). Carriers of the DSP rs2076295*G allele benefitted from nintedanib treatment compared with TT genotype by a longer OS [hazard ratio (HR) = 7.99; 95% confidence interval (CI) = 1.56–40.90; p = 0.013] and a slower decline in lung function (HR = 8.51; 95% CI = 1.68–43.14; p = 0.010). Patients with a TT genotype (rs2076295) benefitted from treatment with pirfenidone by prolonged OS ( p = 0.040; HR = 0.35; 95% CI = 0.13–0.95) compared with nintedanib treatment. Both associations were confirmed by cross-validation analysis. After stratifying by MUC5B rs35705950*T allele carriage, no difference in treatment outcome was observed for nintedanib or pirfenidone ( p = 0.784). In the multivariate model, smoking, age, forced vital capacity (FVC) and DL CO (diffuse lung capacity) at the IPF diagnosis were associated with survival. Conclusion: Our real-world study showed that IPF patients with MUC5B T* allele or DSP G* allele profit from antifibrotic treatment by lower mortability. Moreover, carriers of the DSP rs2076295*G allele benefit from treatment with ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1753-4666 |
| Relation: | https://doi.org/10.1177/17534666211042529; https://doaj.org/toc/1753-4666; https://doaj.org/article/f44baceebf1c45358ab4de31e662b434 |
| DOI: | 10.1177/17534666211042529 |
| الاتاحة: | https://doi.org/10.1177/17534666211042529 https://doaj.org/article/f44baceebf1c45358ab4de31e662b434 |
| رقم الانضمام: | edsbas.19C6C292 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17534666 |
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| DOI: | 10.1177/17534666211042529 |