Genetic Predictors of Long-term Response to Antitumor Necrosis Factor Agents in Pediatric Inflammatory Bowel Disease
Sara Salvador-Martín
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid
Search for more papers by this authorFerrán Bossacoma
Fundació Sant Joan de Déu, Fundació Salut Emporda, Barcelona
Search for more papers by this authorGemma Pujol-Muncunill
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona
Search for more papers by this authorVíctor Manuel Navas-López
Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, IBIMA Multidisciplinary Group for Pediatric Research, Málaga
Search for more papers by this authorCarmen Gallego-Fernández
Pharmacy Department, Hospital Regional Universitario de Málaga, Málaga
Search for more papers by this authorJavier Viada
Department of Pediatric Gastroenterology, Hospital Infantil Universitario Niño Jesús, Madrid
Search for more papers by this authorRosana Muñoz-Codoceo
Department of Pediatric Gastroenterology, Hospital Infantil Universitario Niño Jesús, Madrid
Search for more papers by this authorLorena Magallares
Department of Pediatric Gastroenterology, University Hospital La Paz, Madrid
Search for more papers by this authorEva Martínez-Ojinaga
Department of Pediatric Gastroenterology, University Hospital La Paz, Madrid
Search for more papers by this authorAna Moreno-Álvarez
Pediatric Gastroenterology Unit, Department of Pediatrics, A Coruña University Hospital, A Coruña
Search for more papers by this authorAlfonso Solar-Boga
Pediatric Gastroenterology Unit, Department of Pediatrics, A Coruña University Hospital, A Coruña
Search for more papers by this authorOscar Segarra
Pediatric Gastroenterology Unit, Hospital Universitario Vall d’Hebrón, Barcelona
Search for more papers by this authorSusana Clemente
Pharmacy Service, Hospital Universitario Vall d’Hebrón, Barcelona
Search for more papers by this authorAlejandro Rodriguez-Martinez
Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital Universitario Virgen del Rocio, Seville
Search for more papers by this authorConcepción Alvarez-Vayo
Pharmacy Service, Hospital Universitario Virgen del Rocio, Seville
Search for more papers by this authorInés Loverdos
Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital de Sabadell, Corporació Sanitària Universitària Parc Taulí, Barcelona
Search for more papers by this authorVicente Merino-Bohórquez
UGC Pharmacy Department, Hospital Virgen de la Macarena, Seville
Search for more papers by this authorMaría J. Balboa-Vega
UGC Pediatric Department, Hospital Virgen de la Macarena, Seville
Search for more papers by this authorJosé A. Blanca-García
Pediatric Gastroenterology Unit, Hospital Puerta del Mar, Cadiz
Search for more papers by this authorMaría J. Fobelo
Pharmacy Service, Hospital Virgen de Valme, Sevilla
Search for more papers by this authorAntonio Millán-Jiménez
Pediatric Gastroenteology Unit, Hospital Virgen de Valme, Sevilla
Search for more papers by this authorRuth García-Romero
Pediatric Gastroenterology Unit, Hospital Infantil Miguel Servet, Zaragoza
Search for more papers by this authorCesar Sanchez
Gastroenterology Unit, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid
Search for more papers by this authorMar Tolín
Gastroenterology Unit, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid
Search for more papers by this authorRafael Gonzalez de Caldas
Pediatric Gastroenterology Unit, Hospital Reina Sofía, Córdoba
Search for more papers by this authorFrancisco J. Eizaguirre
Pediatric Gastroenterology Unit, Hospital Universitario Donostia, San Sebastian
Search for more papers by this authorJosé G. Sánchez-Hernandez
Pharmacy Service, Complejo Asistencial Universitario de Salamanca, Salamanca
Search for more papers by this authorRicardo Torres-Peral
Pediatric Gastroenterology Unit, Complejo Asistencial Universitario de Salamanca, Salamanca
Search for more papers by this authorElena Aznal
Pediatric Department, Hospital Virgen del Camino, Pamplona
Search for more papers by this authorXandra García-González
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid
Search for more papers by this authorMaría Sanjurjo-Sáez
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid
Search for more papers by this authorCorresponding Author
Luis A. López-Fernández
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid
Spanish Clinical Research Network, SCReN, Madrid, Spain
Address correspondence and reprint requests to Luis A. López-Fernández, Edificio de Farmacia, Hospital General Universitario Gregorio Marañón, c/Dr. Esquerdo 46, 28007 Madrid, Spain (e-mail: [email protected]).Search for more papers by this authorSara Salvador-Martín
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid
Search for more papers by this authorFerrán Bossacoma
Fundació Sant Joan de Déu, Fundació Salut Emporda, Barcelona
Search for more papers by this authorGemma Pujol-Muncunill
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona
Search for more papers by this authorVíctor Manuel Navas-López
Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, IBIMA Multidisciplinary Group for Pediatric Research, Málaga
Search for more papers by this authorCarmen Gallego-Fernández
Pharmacy Department, Hospital Regional Universitario de Málaga, Málaga
Search for more papers by this authorJavier Viada
Department of Pediatric Gastroenterology, Hospital Infantil Universitario Niño Jesús, Madrid
Search for more papers by this authorRosana Muñoz-Codoceo
Department of Pediatric Gastroenterology, Hospital Infantil Universitario Niño Jesús, Madrid
Search for more papers by this authorLorena Magallares
Department of Pediatric Gastroenterology, University Hospital La Paz, Madrid
Search for more papers by this authorEva Martínez-Ojinaga
Department of Pediatric Gastroenterology, University Hospital La Paz, Madrid
Search for more papers by this authorAna Moreno-Álvarez
Pediatric Gastroenterology Unit, Department of Pediatrics, A Coruña University Hospital, A Coruña
Search for more papers by this authorAlfonso Solar-Boga
Pediatric Gastroenterology Unit, Department of Pediatrics, A Coruña University Hospital, A Coruña
Search for more papers by this authorOscar Segarra
Pediatric Gastroenterology Unit, Hospital Universitario Vall d’Hebrón, Barcelona
Search for more papers by this authorSusana Clemente
Pharmacy Service, Hospital Universitario Vall d’Hebrón, Barcelona
Search for more papers by this authorAlejandro Rodriguez-Martinez
Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital Universitario Virgen del Rocio, Seville
Search for more papers by this authorConcepción Alvarez-Vayo
Pharmacy Service, Hospital Universitario Virgen del Rocio, Seville
Search for more papers by this authorInés Loverdos
Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital de Sabadell, Corporació Sanitària Universitària Parc Taulí, Barcelona
Search for more papers by this authorVicente Merino-Bohórquez
UGC Pharmacy Department, Hospital Virgen de la Macarena, Seville
Search for more papers by this authorMaría J. Balboa-Vega
UGC Pediatric Department, Hospital Virgen de la Macarena, Seville
Search for more papers by this authorJosé A. Blanca-García
Pediatric Gastroenterology Unit, Hospital Puerta del Mar, Cadiz
Search for more papers by this authorMaría J. Fobelo
Pharmacy Service, Hospital Virgen de Valme, Sevilla
Search for more papers by this authorAntonio Millán-Jiménez
Pediatric Gastroenteology Unit, Hospital Virgen de Valme, Sevilla
Search for more papers by this authorRuth García-Romero
Pediatric Gastroenterology Unit, Hospital Infantil Miguel Servet, Zaragoza
Search for more papers by this authorCesar Sanchez
Gastroenterology Unit, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid
Search for more papers by this authorMar Tolín
Gastroenterology Unit, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid
Search for more papers by this authorRafael Gonzalez de Caldas
Pediatric Gastroenterology Unit, Hospital Reina Sofía, Córdoba
Search for more papers by this authorFrancisco J. Eizaguirre
Pediatric Gastroenterology Unit, Hospital Universitario Donostia, San Sebastian
Search for more papers by this authorJosé G. Sánchez-Hernandez
Pharmacy Service, Complejo Asistencial Universitario de Salamanca, Salamanca
Search for more papers by this authorRicardo Torres-Peral
Pediatric Gastroenterology Unit, Complejo Asistencial Universitario de Salamanca, Salamanca
Search for more papers by this authorElena Aznal
Pediatric Department, Hospital Virgen del Camino, Pamplona
Search for more papers by this authorXandra García-González
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid
Search for more papers by this authorMaría Sanjurjo-Sáez
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid
Search for more papers by this authorCorresponding Author
Luis A. López-Fernández
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid
Spanish Clinical Research Network, SCReN, Madrid, Spain
Address correspondence and reprint requests to Luis A. López-Fernández, Edificio de Farmacia, Hospital General Universitario Gregorio Marañón, c/Dr. Esquerdo 46, 28007 Madrid, Spain (e-mail: [email protected]).Search for more papers by this authorThe authors received financial support for the research, authorship, and publication of this article from the following: Ministry of Economy and Competitiveness ISCIII-FIS (grant numbers PI16/00559 and PI19/00792), Consejería de Educación y Deporte de la Comunidad de Madrid (grant numbers PEJ16/MED/AI-1260 and PEJD-2018-PRE/BMD-8665), and Gregorio Marañón Health Research Institute (grant number PRE-2018-2). The study was cofunded by ERDF Funds (FEDER) from the European Commission, “A way of making Europe”.
The authors report no conflicts of interest.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).
ABSTRACT
Objectives:
Inflammatory bowel disease (IBD) is more complex in children and they will have to live with the disease for much longer. For this reason, it is necessary to optimize treatment. The polymorphisms associated with the response to anti-tumor necrosis factor (TNF) drugs in adults with IBD have not been analyzed in children. The aim of the study was to identify genetic variants associated with the long-term response to anti-TNF drugs in children with IBD.
Methods:
An observational, longitudinal, ambispective cohort's study was conducted. We recruited 209 anti-TNF-treated children diagnosed with IBD and genotyped 21 polymorphisms previously studied in adults with Crohn disease (CD) using real-time PCR. The association between single-nucleotide polymorphisms (SNPs) and time-to-failure was analyzed using the log-rank test.
Results:
After multivariate analysis, 3 SNPs in IL10, IL17A and IL6 were significantly associated with response to anti-TNF treatment among patients diagnosed with CD (rs1800872-HR, 4.749 (95% confidence interval [CI] 1.156–19.517), P value < 0.05; rs2275913-HR, 0.320 [95% CI 0.111–0.920], P value < 0.05; and rs10499563-HR, 0.210 [95% CI 0.047–0.947], P value 0.05, respectively). None of these SNPs were associated with response to infliximab in adults diagnosed with CD. Among patients diagnosed with ulcerative colitis (UC), 1 SNP in LY96 was significantly associated with response to anti-TNF treatment (rs-11465996-HR, 10.220 [95% CI 1.849–56.504] P value < 0.05).
Conclusions:
Genotyping of these DNA variants before starting treatment may help to identify children who are long-term responders to anti-TNF drugs, and thus tailor treatment of pediatric IBD.
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