RT Journal Article
T1 Pharmacogenetics of siponimod: A systematic review.
A1 Diaz-Villamarin, Xando
A1 Piñar-Morales, Raquel
A1 Barrero-Hernandez, Francisco Javier
A1 Antunez-Rodriguez, Alba
A1 Cabeza-Barrera, Jose
A1 Moron-Romero, Rocio
K1 CYP2C9
K1 Mayzent
K1 Multiple Sclerosis
K1 Pharmacogenetics
K1 Siponimod
AB 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.
PB Elsevier Masson
YR 2022
FD 2022-08-08
LK http://hdl.handle.net/10668/22048
UL http://hdl.handle.net/10668/22048
LA en
NO Díaz-Villamarín X, Piñar-Morales R, Barrero-Hernández FJ, Antúnez-Rodríguez A, Cabeza-Barrera J, Morón-Romero R. Pharmacogenetics of siponimod: A systematic review. Biomed Pharmacother. 2022 Sep;153:113536.
DS RISalud
RD Apr 11, 2025