1. Pharmacogenetics of trough serum anti‐TNF levels in paediatric inflammatory bowel disease
- Author
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Oscar Segarra, Elena Aznal, Antonio Millán-Jiménez, Francisco J. Eizaguirre, María Jesús Balboa-Vega, Gemma Pujol-Muncunill, Alejandro Rodriguez-Martinez, Rafael González de Caldas, Concepción Alvarez-Vayo, Carmen Gallego-Fernández, Judith Abarca-Zabalía, Susana Clemente, Rosana Muñoz-Codoceo, Mar Tolin, Javier Viada, Víctor Manuel Navas-López, Ana Moreno-Álvarez, César Sánchez, María Sanjurjo-Sáez, Inés Loverdos, Lorena Magallares, José Germán Sánchez-Hernández, Sara Salvador-Martín, Alfonso Solar-Boga, Eva Martínez-Ojinaga, Ferrán Bossacoma, Luis A. López-Fernández, Vicente Merino-Bohórquez, R. García-Romero, and José A. Blanca-García
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Adolescent ,030226 pharmacology & pharmacy ,Inflammatory bowel disease ,Gastroenterology ,pharmacokinetic-pharmacodynamic ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Internal medicine ,Adalimumab ,Humans ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Child ,Genotyping ,Fisher's exact test ,biomarkers ,pharmacogenomics ,Pharmacology ,business.industry ,Inflammatory Bowel Diseases ,medicine.disease ,Infliximab ,gastroenterology, children ,Regimen ,Pharmacogenetics ,symbols ,Tumor Necrosis Factor Inhibitors ,Tumor necrosis factor alpha ,business ,medicine.drug - Abstract
AIMS: Identifying DNA variants associated with trough serum anti-tumour necrosis factor (TNF) levels could predict response to treatment in inflammatory bowel disease (IBD). To date, no specific studies have been performed in children. The aim of this study was to identify genetic variants associated with trough serum anti-TNF levels and whether these variants are differential markers for infliximab and adalimumab. METHODS: We included 154 children (age < 18 years) from 17 hospitals who had been diagnosed with IBD and actively treated with infliximab or adalimumab. Twenty-one polymorphisms were genotyped using real-time PCR. Trough serum anti-TNF levels were measured using enzyme-linked immunosorbent assay (ELISA). The association between DNA polymorphisms and the therapeutic range or the absolute values of anti-TNF drugs was analysed by Fisher exact test, student's t-test and logistic regression. RESULTS: The variants rs5030728 (TLR4) and rs11465996 (LY96) were associated with subtherapeutic infliximab levels. rs1816702 (TLR2) was associated with supratherapeutic levels and rs3397 (TNFRSF1B) with subtherapeutic levels of adalimumab (P < .05). In addition, rs1816702 (TLR2) and rs2569190 (CD14) were associated with absolute values of trough serum adalimumab, and rs2569190 (CD14) was associated with absolute values of trough serum adalimumab and infliximab (P < .05). CONCLUSION: Genotyping of these DNA variants before starting treatment may help to select the best anti-TNF drug in paediatric patients. The SNP rs1816702 is the most promising marker for tailoring the anti-TNF regimen in children with IBD. For the first time, DNA variants are associated with trough serum anti-TNF levels.
- Published
- 2020
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