Associations of SLCO gene polymorphisms with perampanel response and plasma concentrations in patients: a longitudinal retrospective real-world study in refractory epilepsy.

SLCO1A2, SLCO1B1

Polymorphisms in SLCO1A2 and SLCO1B1 are associated with perampanel efficacy and presented as factors influencing its plasma concentrations.

This longitudinal retrospective real-world study analyses the correlation between polymorphisms of the SLCO genes and both the efficacy and the plasma concentrations of perampanel in paediatric patients with refractory epilepsy. SLCO genotypes were determined by first-generation Sanger sequencing and perampanel plasma concentrations by ultra-performance liquid chromatography-tandem mass spectrometry. Perampanel was effective in 64.3% of patients (74 of 115); the SLCO1A2 rs4149000, SLCO1B1 rs2306283 and rs12422149 polymorphisms were significantly associated with this efficacy, and age, epilepsy duration, concomitant medications and the SLCO1A2 rs4149000 polymorphism were important predictors of effective seizure control (p < 0.05). In children on the once-daily regimen, perampanel plasma concentrations were significantly higher in the group in which treatment was effective than in the group in which it was not (598.5 ± 390.2 vs 452.9 ± 296.5 ng/mL; p = 0.027). The authors conclude that SLCO polymorphisms are important predictors of seizure control on perampanel and factors influencing its plasma concentrations, and that SLCO genotyping combined with concentration monitoring offers a promising treatment strategy for Chinese patients with refractory epilepsy.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The abstract gives no effect size: three polymorphisms are said to be associated with efficacy in 115 patients, with no indication of by how much or in which direction, how many loci were tested, or whether multiple testing was corrected. The efficacy endpoint is not defined, and the only quantified concentration difference (598.5 vs 452.9 ng/mL, confined to the once-daily subgroup) comes with wide standard deviations, which rules out deriving a target concentration from it. This is a retrospective association study in a Chinese population: it does not show that a treatment choice guided by SLCO genotype improves seizure control.

Analysis by Dr Thibaut Benquey