RELATIONSHIP BETWEEN ADALIMUMAB, PHARMACOKINETICS AND VITAMIN D-RELATED MARKERS in Digestive and Liver Disease
2020
ASL Città di Torino
Tipo pubblicazione
Conference Abstract
Autori/Collaboratori (6)Vedi tutti...
D'Avolio A
Saracco GM
Astegiano M
et alii...
Abstract
Background and aim: Vitamin D (VIT D) controls innate and adaptive immunity and regulates many genes involved in drug metabolism through its receptor (VDR). Adalimumab (ADA) is a monoclonal antibody used for treatment of Inflammatory Bowel Disease (IBD); measurement of trough level is useful to monitor clinical outcome. We analyzed Single Nucleotide Polymorphisms (SNPs) of VIT D related genes to associate VIT D kinetic and genetic information with drug pharmacokinetics. Materials and methods: This prospective study was carried out on a cohort of outpatients (pts) affected by IBD who started adalimumab. Plasma drug concentration was measured at 3 months and at 12 months immediately before drug administration (trough levels) with validated ELISA kits. Values of 25-VIT D and 1,25-VIT D were measured with ELISA and with LIAISON® XL, respectively. SNPs were investigated by TaqMan Real-Time PCR Assay. Results: Fifty pts affected by Crohn's disease (N=47) or ulcerative colitis (N=3) were evaluated. VDR Cdx2 affected 1,25-VIT D at baseline (p=0.014): AA genotype had a median level of 34.6 µg/mL (31.3-38.6 µg/mL), whereas AG/GG pts had 41.9 µg/mL (36.2-49.3 µg/mL). CYP24A1 3999 influenced 25-VIT D at 3 months of therapy (p=0.006): CC/CT pts had a median level of 21.2 µg/mL (11.7-27.3 µg/mL) vs. TT pts which had 37.0 µg/mL (28.0-43.7 µg/mL). CYP24A1 22776 affected 1,25-VIT D at 3 months (p=0.047): CC genotype had median level of 53.4 µg/mL (42.2-63.1 µg/mL) vs. CT/TT ones with 41.7 µg/mL (37.5-49.1 µg/mL). 1,25 VIT D concentrations at 12 months were influenced by VDR TaqI genotypes: TT genotype pts had 58.4 µg/mL (55.1-63.2 µg/mL) median levels vs. TC/CC ones with 45.2 µg/mL (41.6-47.2 µg/mL). ADA levels at 3 months were influenced by VDR TaqI TC/CC (p=0.038): TT pts had a median value of 6.1 µg/mL (3.6-6.5 µg/mL), whereas TC/CC pts had 10.5 µg/mL (6.1-14.3 µg/mL). ADA concentrations at 3 month correlated with 1,25 VD levels at 3 months (p=0.031, P
DOI : 10.1016/S1590-8658(20)30759-3
Keywords
adalimumab; colecalciferol 24 hydroxylase; endogenous compound; vitamin D; vitamin D receptor; adult; clinical article; cohort analysis; conference abstract; controlled study; Crohn disease; drug therapy; ELISA kit; female; gender; genotype; human; human tissue; male; outpatient; pharmacokinetics; prospective study; real time polymerase chain reaction; single nucleotide polymorphism; ulcerative colitis; vitamin blood level;