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@article{1801288,
author = {Doubková, Martina and Kriegova, Eva and Littnerová, Simona and Schneiderova, Petra and Sterclova, Martina and Bartos, Vladimir and Plackova, Martina and Zurkova, Monika and Bittenglova, Radka and Lostakova, Vladimira and Siskova, Lenka and Lisa, Pavlina and Suldova, Hana and Doubek, Michael and Psikalova, Jana and Snizek, Tomas and Musilova, Pavlina and Vasakova, Martina},
article_location = {LONDON},
article_number = {September 2021},
doi = {http://dx.doi.org/10.1177/17534666211042529},
keywords = {antifibrotic treatment; desmoplakin; IPF; mucin 5; single nucleotide polymorphisms},
language = {eng},
issn = {1753-4658},
journal = {THERAPEUTIC ADVANCES IN RESPIRATORY DISEASE},
title = {DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study},
url = {https://journals.sagepub.com/doi/10.1177/17534666211042529},
volume = {15},
year = {2021}
}
TY - JOUR
ID - 1801288
AU - Doubková, Martina - Kriegova, Eva - Littnerová, Simona - Schneiderova, Petra - Sterclova, Martina - Bartos, Vladimir - Plackova, Martina - Zurkova, Monika - Bittenglova, Radka - Lostakova, Vladimira - Siskova, Lenka - Lisa, Pavlina - Suldova, Hana - Doubek, Michael - Psikalova, Jana - Snizek, Tomas - Musilova, Pavlina - Vasakova, Martina
PY - 2021
TI - DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study
JF - THERAPEUTIC ADVANCES IN RESPIRATORY DISEASE
VL - 15
IS - September 2021
SP - 1-16
EP - 1-16
PB - SAGE PUBLICATIONS LTD
SN - 17534658
KW - antifibrotic treatment
KW - desmoplakin
KW - IPF
KW - mucin 5
KW - single nucleotide polymorphisms
UR - https://journals.sagepub.com/doi/10.1177/17534666211042529
N2 - 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 DLCO (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 nintedanib, and TT genotype from treatment with pirfenidone. MUC5B rs35705950 did not impact the outcome of treatment with either nintedanib or pirfenidone. Our single-registry pilot study should be confirmed with an independent patient cohort.
ER -
DOUBKOVÁ, Martina, Eva KRIEGOVA, Simona LITTNEROVÁ, Petra SCHNEIDEROVA, Martina STERCLOVA, Vladimir BARTOS, Martina PLACKOVA, Monika ZURKOVA, Radka BITTENGLOVA, Vladimira LOSTAKOVA, Lenka SISKOVA, Pavlina LISA, Hana SULDOVA, Michael DOUBEK, Jana PSIKALOVA, Tomas SNIZEK, Pavlina MUSILOVA a Martina VASAKOVA. DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study. \textit{THERAPEUTIC ADVANCES IN RESPIRATORY DISEASE}. LONDON: SAGE PUBLICATIONS LTD, 2021, roč.~15, September 2021, s.~1-16. ISSN~1753-4658. Dostupné z: https://dx.doi.org/10.1177/17534666211042529.
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