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DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study

M. Doubkova, E. Kriegova, S. Littnerova, P. Schneiderova, M. Sterclova, V. Bartos, M. Plackova, M. Zurkova, R. Bittenglova, V. Lostaková, L. Siskova, P. Lisa, H. Suldova, M. Doubek, J. Psikalova, T. Snizek, P. Musilova, M. Vasakova

. 2021 ; 15 (-) : 17534666211042529. [pub] -

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22012581

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

Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Immunology Faculty of Medicine and Dentistry Palacky University in Olomouc and University Hospital Olomouc Olomouc Czech Republic

Department of Pneumology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Pneumology Faculty of Medicine in Hradec Králové Charles University Prague Czech Republic

Department of Pneumology Faculty of Medicine University Hospital in Ostrava Ostrava Czech Republic

Department of Pulmonology and Physiology Faculty of Medicine Masaryk University and University Hospital Brno Jihlavská 20 625 00 Brno Czech Republic

Department of Respiratory Diseases Faculty of Medicine in Pilsen Charles University and University Hospital Pilsen Pilsen Czech Republic

Department of Respiratory Diseases Jihlava Hospital Jihlava Czech Republic

Department of Respiratory Diseases Tomáš Baťa Regional Hospital Zlín Czech Republic

Department of Respiratory Medicine 1st Faculty of Medicine Charles University and Thomayer Hospital Prague Czech Republic

Department of Respiratory Medicine Faculty of Medicine and Dentistry Palacky University in Olomouc and University Hospital Olomouc Olomouc Czech Republic

Institute of Biostatistics and Analyses Masaryk University Brno Czech Republic

PneumoAllergology Department Kroměříž Hospital Kromeriz Czech Republic

Pulmonary Department České Budějovice Hospital Ceske Budejovice Czech Republic

Citace poskytuje Crossref.org

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$a Doubkova, Martina $u Department of Pulmonology and Physiology, Faculty of Medicine, Masaryk University and University Hospital Brno, Jihlavská 20, 625 00 Brno, Czech Republic $1 https://orcid.org/0000000165363134 $7 xx0076294
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$a DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study / $c M. Doubkova, E. Kriegova, S. Littnerova, P. Schneiderova, M. Sterclova, V. Bartos, M. Plackova, M. Zurkova, R. Bittenglova, V. Lostaková, L. Siskova, P. Lisa, H. Suldova, M. Doubek, J. Psikalova, T. Snizek, P. Musilova, M. Vasakova
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$a 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 m $a 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. $a BACKGROUND The antifibrotic drugs nintedanib and pirfenidone are used for the treatment of idiopathic pulmonary fibrosis IPF We analysed the association of common profibrotic polymorphisms in MUC5B mucin 5B rs35705950 and DSP desmoplakin rs2076295 on antifibrotic treatment outcomes in IPF METHODS MUC5B rs35705950 and DSP rs2076295 were assessed in IPF patients n 210 139 men 71 women from
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$a Kriegova, Eva $u Department of Immunology, Faculty of Medicine and Dentistry, Palacky University in Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
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$a Littnerova, Simona $u Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic
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$a Schneiderova, Petra $u Department of Immunology, Faculty of Medicine and Dentistry, Palacky University in Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
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$a Sterclova, Martina $u Department of Respiratory Medicine, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
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$a Bartos, Vladimir $u Department of Pneumology, Faculty of Medicine in Hradec Králové, Charles University, Prague, Czech Republic
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$a Plackova, Martina $u Department of Pneumology, Faculty of Medicine, University Hospital in Ostrava, Ostrava, Czech Republic
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$a Zurkova, Monika $u Department of Respiratory Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
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$a Bittenglova, Radka $u Department of Respiratory Diseases, Faculty of Medicine in Pilsen, Charles University and University Hospital Pilsen, Pilsen, Czech Republic
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$a Lostaková, Vladimira $u Department of Respiratory Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
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$a Siskova, Lenka $u Department of Respiratory Diseases, Tomáš Baťa Regional Hospital, Zlín, Czech Republic
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$a Lisá, Pavlína $u Department of Pneumology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic $7 xx0310633
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$a Suldova, Hana $u Pulmonary Department, České Budějovice Hospital, Ceske Budejovice, Czech Republic
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$a Doubek, Michael $u Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic
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$a Psikalova, Jana $u PneumoAllergology Department, Kroměříž Hospital, Kromeriz, Czech Republic
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$a Snizek, Tomas $u Department of Respiratory Diseases, Jihlava Hospital, Jihlava, Czech Republic
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$a Musilova, Pavlina $u Department of Respiratory Diseases, Jihlava Hospital, Jihlava, Czech Republic
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$a Vasakova, Martina $u Department of Respiratory Medicine, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
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