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. 2021 Feb;87(2):447-457.
doi: 10.1111/bcp.14400. Epub 2020 Jul 1.

Pharmacogenetics of trough serum anti-TNF levels in paediatric inflammatory bowel disease

Sara Salvador-Martín  1 , Gemma Pujol-Muncunill  2 , Ferran Bossacoma  3 , Víctor Manuel Navas-López  4 , Carmen Gallego-Fernández  5 , Oscar Segarra  6 , Susana Clemente  7 , Rosana Muñoz-Codoceo  8 , Javier Viada  8 , Lorena Magallares  9 , Eva Martínez-Ojinaga  9 , Ana Moreno-Álvarez  10 , Alfonso Solar-Boga  10 , Inés Loverdos  11 , Vicente Merino-Bohórquez  12 , María Jesús Balboa-Vega  13 , Alejandro Rodriguez-Martinez  14 , Concepción Alvarez-Vayo  15 , Cesar Sanchez  16 , Mar Tolin  16 , José Antonio Blanca-García  17 , Ruth García-Romero  18 , Francisco Javier Eizaguirre  19 , José Germán Sánchez-Hernandez  20 , Rafael Gonzalez de Caldas  21 , Antonio Millán-Jimenez  22 , Elena Aznal  23 , Judith Abarca-Zabalía  1 , María Sanjurjo-Sáez  1 , Luis Andrés López-Fernández  1   24
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Free article

Pharmacogenetics of trough serum anti-TNF levels in paediatric inflammatory bowel disease

Sara Salvador-Martín et al. Br J Clin Pharmacol. 2021 Feb.
Free article

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.

Keywords: biomarkers; gastroenterology, children; pharmacogenomics; pharmacokinetic-pharmacodynamic.

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References

REFERENCES

    1. Loddo I, Romano C. Inflammatory bowel disease: genetics, epigenetics, and pathogenesis. Front Immunol. 2015;6:551.
    1. Grover Z. Predicting and preventing complications in children with inflammatory bowel disease. Transl Pediatr. 2019;8(1):70-76.
    1. Ishige T. Growth failure in pediatric onset inflammatory bowel disease: mechanisms, epidemiology, and management. Transl Pediatr. 2019;8(1):16-22.
    1. Corica D, Romano C. Biological therapy in pediatric inflammatory bowel disease. J Clin Gastroenterol. 2017;51(2):100-110.
    1. Van Assche G, Vermeire S, Rutgeerts P. Infliximab therapy for patients with inflammatory bowel disease: 10 years on. Eur J Pharmacol. 2009;623:S17-S25.

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