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One year of experience with combined pharmacokinetic/pharmacogenetic monitoring of anti-TNF alpha agents: a retrospective study

The Pharmacogenomics Journal volume 23, pages 112–118 (2023)Cite this article

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A Correction to this article was published on 25 May 2023

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Abstract

Anti-tumor necrosis factor alpha (anti-TNFα) inhibitors are used extensively for the management of moderate to severe inflammatory bowel disease (IBD) in both adult and pediatric patients. Unfortunately, not all patients show an optimal response to induction therapy, while others lose their response over time for reasons yet poorly understood. We report on a pharmacokinetic/pharmacogenetic approach to monitor the therapy with anti-TNFα in a real-world cohort of seventy-nine pediatric patients affected by IBD that was analyzed retrospectively. We evaluated plasma concentrations of infliximab, adalimumab, and related anti-drug antibodies (ADAs), and single nucleotide polymorphisms (SNPs) in genes involved in immune processes and inflammation on the anti-TNFα response. We found a significant association between the SNP in TNFα promoter (−308G>A) and clinical remission without steroids in patients on infliximab therapy. Additionally, a potential connection between HLA-DQA1*05 genetic variant carriers and a higher risk of anti-TNFα immunogenicity emerged.

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Fig. 1: Infliximab and adalimumab concentrations over time.

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Data availability

The data that support the findings of this study are available from the corresponding author, EC, upon reasonable request.

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Authors and Affiliations

  1. Unit of Clinical Pharmacology, ASST Fatebenefratelli Sacco, University Hospital, Milano, Italy

    Stefania Cheli, Diego Savino & Dario Cattaneo

  2. Clinical Epidemiology and Biometry Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Annalisa De Silvestri

  3. Pediatric Hepatology, Gastroenterology and Transplantation Unit, ASST Papa Giovanni XXIII, Bergamo, Italy

    Lorenzo Norsa & Naire Sansotta

  4. Pediatric Department, “Vittore Buzzi” Children’s Hospital, University of Milan, Milano, Italy

    Francesca Penagini & Dario Dilillo

  5. Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy

    Roberto Panceri & Giovanna Zuin

  6. Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, Italy

    Emilio Clementi

  7. Clinical Pharmacology Unit, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Università degli Studi di Milano, Milan, Italy

    Emilio Clementi

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Contributions

SC and GZ were responsible for the conception and design of the analysis. SC and DS verified the analytical methods and performed the experiments. AD contributed to the statistical analysis of the sample data. LN, NS, FP, DD, RP, and GZ collaborated in patient management and clinical presentation. DC contributed to study design, data analysis, and manuscript writing. EC directed and supervised the study and the writing of the manuscript. All authors provided critical feedback and contributed to the manuscript.

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Correspondence to Emilio Clementi.

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Cheli, S., Savino, D., De Silvestri, A. et al. One year of experience with combined pharmacokinetic/pharmacogenetic monitoring of anti-TNF alpha agents: a retrospective study. Pharmacogenomics J 23, 112–118 (2023). https://doi.org/10.1038/s41397-023-00304-z

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