A Genetic Variation in the Neonatal Fc-Receptor Affects Anti-TNF Drug Concentrations in Inflammatory Bowel Disease
| Autor: | Ann Gils, Marc Ferrante, Willem-Jan Wollants, Severine Vermeire, Erwin Dreesen, Thomas Billiet, Isabelle Cleynen, Gert Van Assche |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Drug Pharmacogenomic Variants media_common.quotation_subject Anti-Inflammatory Agents Minisatellite Repeats Receptors Fc Inflammatory bowel disease Cohort Studies Young Adult 03 medical and health sciences 0302 clinical medicine Neonatal Fc receptor Gastrointestinal Agents Genetic variation medicine Humans Retrospective Studies media_common Hepatology Tumor Necrosis Factor-alpha Anti-TNF drug business.industry Histocompatibility Antigens Class I Adalimumab Gastroenterology Middle Aged Inflammatory Bowel Diseases medicine.disease Infliximab 030104 developmental biology Area Under Curve Immunology Linear Models Female 030211 gastroenterology & hepatology business |
| Zdroj: | American Journal of Gastroenterology. 111:1438-1445 |
| ISSN: | 0002-9270 |
| DOI: | 10.1038/ajg.2016.306 |
| Popis: | Ample evidence exists that Anti-tumor necrosis factor (TNF) concentrations during induction determine short and long-term outcome in inflammatory bowel disease (IBD). We investigated if a variable number of tandem repeats (VNTR) polymorphism in the neonatal Fc-receptor (FcRn), responsible for extending half-life of IgG, influences anti-TNF concentrations in patients with IBD.Retrospective single-center study, including a cohort of 395 infliximab (IFX) naive IBD patients treated with IFX 5 mg/kg on weeks 0, 2, and 6 and a second cohort of 139 adalimumab naive patients, treated with adalimumab 160-80-40 mg on weeks 0, 2, and 4. Area under the serum anti-TNF concentration-time curve (AUC), from week 2 and 6 for IFX and week 2 and 4 for adalimumab, was used to identify factors influencing these drug concentrations.The VNTR2/VNTR3 genotype was associated with a 14% lower IFX AUC compared with patients homozygous for VNTR3/VNTR3 (P=0.03), although this effect became apparent only when immunogenicity (26% lower concentrations, P=9 × 10The VNTR2/3 genotype in the FcRn gene is associated with lower IFX but also lower adalimumab drug exposure during induction in patients with IBD. Previously identified pharmacokinetic modifying factors were confirmed. Identifying risk factors in patients is important as higher induction doses may be needed to ensure optimal disease outcome. |
| Databáze: | OpenAIRE |
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