Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
Por:
Salvador-Martín S, Raposo-Gutiérrez I, Navas-López VM, Gallego-Fernández C, Moreno-Álvarez A, Solar-Boga A, Muñoz-Codoceo R, Magallares L, Martínez-Ojinaga E, Fobelo MJ, Millán-Jiménez A, Rodriguez-Martinez A, Vayo CA, Sánchez C, Tolin M, Bossacoma F, Pujol G, González de Caldas R, Loverdos I, Blanca-García JA, Segarra O, Eizaguirre FJ, García-Romero R, Merino-Bohórquez V, Sanjurjo-Sáez M and López-Fernández LA
Publicada:
1 may 2020
Ahead of Print:
9 may 2020
Resumen:
Around a 20-30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2(-Ct) method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.
Filiaciones:
Salvador-Martín S:
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain
Raposo-Gutiérrez I:
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain
Navas-López VM:
Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, IBIMA Multidisciplinary Group for Pediatric Research, 29010 Málaga, Spain
Gallego-Fernández C:
Pharmacy Department, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain
Moreno-Álvarez A:
Pediatric Gastroenterology Unit, Department of Pediatrics, A Coruña University Hospital, 15006 A Coruña, Spain
Solar-Boga A:
Pediatric Gastroenterology Unit, Department of Pediatrics, A Coruña University Hospital, 15006 A Coruña, Spain
Muñoz-Codoceo R:
Department of Pediatric Gastroenterology, Hospital Infantil Universitario Niño Jesús, 28009 Madrid, Spain
Magallares L:
Department of Pediatric Gastroenterology, University Hospital La Paz, 28046 Madrid, Spain
Martínez-Ojinaga E:
Department of Pediatric Gastroenterology, University Hospital La Paz, 28046 Madrid, Spain
Fobelo MJ:
Pharmacy Service, Hospital Virgen de Valme, 41014 Sevilla, Spain
Millán-Jiménez A:
Pediatric Gastroenterology Unit, Hospital Virgen de Valme, 41014 Sevilla, Spain
Rodriguez-Martinez A:
Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital Universitario Virgen del Rocio, 41013 Seville, Spain
Vayo CA:
Pharmacy Service, Hospital Universitario Virgen del Rocio, 41013 Seville, Spain
Sánchez C:
Gastroenterology Unit, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain
Tolin M:
Gastroenterology Unit, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain
Bossacoma F:
Fundació Sant Joan de Déu, Fundació Salut Emporda, 08950 Barcelona, Spain
Pujol G:
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
González de Caldas R:
Pediatric Gastroenterology Unit, Hospital Reina Sofía, 14004 Córdoba, Spain
Loverdos I:
Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital de Sabadell, Corporació Sanitària Universitària Parc Taulí, 08208 Barcelona, Spain
Blanca-García JA:
Pediatric Gastroenterology Unit, Hospital Puerta del Mar, 11009 Cadiz, Spain
Segarra O:
Pediatric Gastroenterology Unit, Hospital Universitario Vall d'Hebrón, 08035 Barcelona, Spain
Eizaguirre FJ:
Pediatric Gastroenterology Unit, Hospital Universitario Donostia, 20014 San Sebastián, Spain
García-Romero R:
Pediatric Gastroenterology Unit, Hospital Infantil Miguel Servet, 50009 Zaragoza, Spain
Merino-Bohórquez V:
UGC Pharmacy Department, Hospital Virgen de la Macarena, 41009 Sevilla, Spain
Sanjurjo-Sáez M:
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain
López-Fernández LA:
Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain
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