@misc{10481/77829,
year = {2022},
month = {8},
url = {https://hdl.handle.net/10481/77829},
abstract = {Multiple sclerosis is a chronic inflammatory neurological disease, and siponimod (Mayzent) is the first oral
treatment option for adult patients with secondary progressive multiple sclerosis. We performed a systematic
review of the pharmacogenetics of Siponimod, and we found that (430 C>T; rs1799853) and CYP2C9 * 3 (1075
A>C; rs1057910), both translated no-function alleles, have been related to a lower metabolism of siponimod by
CYP2C9 enzyme. The FDA-approved drug label and EMA risk management plan for siponimod require testing
patients for CYP2C9 genotype before treatment starts. The FDA drug label states that siponimod is contraindicated
in patients carrying a CYP2C9 * 3/* 3 genotype, and a daily maintenance dose of 1 mg in patients with
CYP2C9 * 1/* 3 and * 2/* 3 genotypes. The EMA reported the potential long-term safety implications in CYP2C9
poor metabolizer patients treated with this drug. Based on this systematic review we concluded that CYP2C9
SNPs influence on siponimod response might be stated by assessing not only CYP2C9 * 2 and CYP2C9 * 3 but
other genetic variants resulting in CYP2C9 IM/PM status. CYP2C9 IM phenotype translated from the CYP2C9 * 2
genotype should be revised since it is contradictory compared to other CYP2C9 no-function alleles, and CYP2C9
* 2 might be excluded from PGx testing recommendation before treatment starts with siponimod since it is not
translated into a therapeutic recommendation.},
publisher = {Elsevier},
keywords = {Multiple sclerosis},
keywords = {Pharmacogenetics},
keywords = {Siponimod},
keywords = {CYP2C9},
keywords = {Mayzent},
title = {Pharmacogenetics of siponimod: A systematic review},
doi = {10.1016/j.biopha.2022.113536},
author = {Díaz Villamarín, Xando and Piñar Morales, Raquel and Barrero Hernández, Francisco Javier and Antúnez Rodríguez, Alba and Cabeza Barrera, José and Morón Romero, María Rocío},
}