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Pharmacogenetics of trough serum anti‐TNF levels in paediatric inflammatory bowel disease
Author(s) -
SalvadorMartín Sara,
PujolMuncunill Gemma,
Bossacoma Ferran,
NavasLópez Víctor Manuel,
GallegoFernández Carmen,
Segarra Oscar,
Clemente Susana,
MuñozCodoceo Rosana,
Viada Javier,
Magallares Lorena,
MartínezOjinaga Eva,
MorenoÁlvarez Ana,
SolarBoga Alfonso,
Loverdos Inés,
MerinoBohórquez Vicente,
BalboaVega María Jesús,
RodriguezMartinez Alejandro,
AlvarezVayo Concepción,
Sanchez Cesar,
Tolin Mar,
BlancaGarcía José Antonio,
GarcíaRomero Ruth,
Eizaguirre Francisco Javier,
SánchezHernandez José Germán,
Caldas Rafael Gonzalez,
MillánJimenez Antonio,
Aznal Elena,
AbarcaZabalía Judith,
SanjurjoSáez María,
LópezFernández Luis Andrés
Publication year - 2021
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14400
Subject(s) - adalimumab , infliximab , medicine , etanercept , trough level , inflammatory bowel disease , genotyping , gastroenterology , pharmacogenetics , immunology , therapeutic drug monitoring , tnf inhibitor , tumor necrosis factor alpha , genotype , pharmacology , disease , pharmacokinetics , biology , transplantation , gene , tacrolimus , biochemistry
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.