Objective To analyze the correlation between HLA-A and B genotypes and maculopapular exanthema (MPE) caused by Carbamazepine (CBZ) and Oxcarbazepine (OXC), and to explore the genetic risk factors of MPE. Methods Patients with MPE (rash group) and patients without MPE (non-rash group) after taking CBZ or OXC were retrospectively collected from January 2016 to October 2021 in the Second Affiliated Hospital of Guangzhou Medical University. DNA was extracted from peripheral blood. HLA-A and HLA-B alleles were sequenced by high resolution sequencing, and a case-control study was conducted to analysis the correlations between MPE and HLA genotypes. Results A total of 100 patients with CBZ-MPE, 100 patients with CBZ-tolerant, 50 patients with OXC-MPE, and 50 patients with OXC-tolerant were collected. There was no significant difference in age and sex between CBZ, OXC rash groups and non-rash groups The average latency of CBZ-rash group was (11.31±11.00) days and their average dosage was (348.46±174.10) mg; the average latency of OXC-rash group was (11.67±10.34) days and their average dosage was (433.52±209.22) mg [equivalent to CBZ (289.01±139.48 mg)], showing no significant difference in latency and dosage between CBZ and OXC (P>0.05). The positive rates of HLA-A*24:02 and A*30:01 in CBZ-rash group were 28% and 6%, respectively, which were significantly higher than those in CBZ-non rash group (16% and 0%, both P=0.04). The positive rate of HLA-B*40:01 in CBZ-rash group was 18%, which was significantly lower than that in CBZ-non rash group (40%, P<0.001). No association between HLA-A or B genotype and OXC-rash was found yet. When pooled, it was still found that the positive rates of HLA-A*24:02 and A*30:01 in the rash group were higher than those in the non-rash group, while the positive rate of HLA-B*40:01 in the rash group was lower than that in the non-rash group, and the difference was statistically significant (P<0.05). Conclusions HLA-A*24:02 and A*30:01 were associated with MPE caused by CBZ, and may be common risk factors for aromatic antiepileptic drugs.
Epilepsy (EP) is one of the most common chronic nervous system disease in childhood and adolescence, with a prevalence rate of 7.6‰. About 3/4 of epilepsy patients begin to get sick in childhood. At present, there are many ways to treat epilepsy, such as oral anti-seizure medications (ASMs), surgical treatment, ketogenic diet, etc. However, ASMs are the preferred treatment for most epilepsy patients and the most important and basic treatment. Oxcarbazepine (OXC) and Lacosamide (LCM) are both sodium channel blockers. The former is a second-generation ASMs, a fast sodium channel blocker, while the latter is a third-generation ASMs, a slow sodium channel blocker. The rapid inactivation of sodium channel is mediated by the inner pore ball chain mechanism in milliseconds, which is helpful to the termination of action potential and the regulation of refractory period. It is the main inactivation mode under normal physiological conditions. Different from the rapid inactivation of sodium channels, the slow inactivation is in seconds per minute, which may involve the rearrangement of the inner pore structure and increase the excitability of the action potential threshold regulating membrane. Generally, under pathological conditions, sodium channels are more likely to enter the slow inactivation state. Now, OXC and LCM have been approved by the US Food and Drug Administration, the European Union Drug Administration, and the National Drug Administration of China for monotherapy or additive therapy of focal origin (with or without secondary generalized seizures) in epilepsy patients aged 4 years and above. This article will focus on the pharmacokinetics, efficacy, and safety of LCM and OXC in the treatment of childhood epilepsy.
ObjectiveTo compare the efficacy and safety of perampanel (PER) and oxcarbazepine (OXC) monotherapy in the treatment of newly diagnosed focal epilepsy in adults. Methods A total of 62 adult patients with focal epilepsy, aged 18~79 years old, with an average age of (40.53±16.69) years, were enrolled from Qingyuan People’s Hospital between August 2021 and October 2022 and randomly divided into PER group and OXC groups. Both groups were followed up for 12 months and assessed for seizure free rate, effective rate, drug retention rate, and adverse reactions at 3, 6, and 12th months. ResultsThe results showed that the seizure free rate, effective rate, and drug retention rate in the PER group were 62.5%, 71.9% and 87.5% at 3 months, respectively, and 53.1%, 65.6% and 75.0% at 6 months respectively. In the OXC group, the seizure free rate, effective rate, and drug retention rate were 70.0%, 86.7%, and 93.3% at 3 months, respectively, and 66.7%, 73.3% and 83.3% at 6 months, respectively. At 12 months, the seizure free rate, effective rate and retention rate of the PER group were 43.8%, 46.9%, and 53.1%, respectively; The seizure free rate, effective rate, and retention rate of OXC group were 66.7%, 66.7%, and 70.0%, respectively. The incidence of adverse reactions in the PER group and OXC group was 15.6% and 16.7%, respectively. The most common adverse reactions in both groups were dizziness and drowsiness, with no serious adverse events. ConclusionPER and OXC monotherapy demonstrated similar efficacy and safety in the treatment of newly diagnosed adult focal epilepsy, and both drugs can be used as safe and effective treatment options.