ObjectiveThe aim of this study was to investigate the pathogenesis of AED-induced SJS/TEN across the spectrum of HLA-A, -B and -DRB1 alleles, and to explore the different clinical characteristics of patients with and without the HLA-B*15:02 allele in the SJS/TEN group. MethodsA total of twenty-three patients exhibiting AED-induced SJS/TEN (16 CBZ-SJS/TEN, seven LTG-SJS/TEN) and fifty-two patients who exhibited tolerance to AEDs were recruited. High-resolution HLA genotyping was performed to estimate the prevalence of the HLA-A, -B and -DRB1 alleles for each subject. Patients in the SJS/TEN group were further divided to positive HLA-B*15:02 allele group and negative HLA-B*15:02 allele group depending on whether carrying the HLA-B*15:02 allele, and the clinical feathers were compared between the two groups. ResultsNine of twenty-three patients (39%) in the SJS/TEN group were male, and the mean age of this group was 32 (8-68) years old. Twenty-eight of fifty-four (54%) patients in the tolerant group were male, and the mean age of the tolerant group was 28 (9-64) years old.Fourteen subjects in the SJS/TEN group carried the HLA-B*15:02 allele, whereas only four subjects (7.7%) in the AED-tolerant group carried this allele; the carrier rate of HLA-B*15:02 was significantly different between the groups (P<0.001). Among the fourteen patients who carried the HLA-B*15:02 allele in the SJS/TEN group, composing the positive HLA-B*15:02 allele group, eight patients (57.1%) were female, whereas six of nine patients in the negative HLA-B*15:02 allele group were female. The difference of the gender didn't have statistical significance between the two groups, nor did the other clinical characteristics, including mean age, the dosage of the AEDs, the interval from the drug administration to the onset of the SJS/TEN, fever, allergic history, abnormal MRI and abnormal EEG results. ConclusionsThe pathogenesis of AED-induced SJS/TEN is a complex process, which may involve one or more alleles. The HLA-B*15:02 allele may be a genetic susceptibility factor of the AED-induced SJS/TEN. However, we didn't find significant difference of the clinical characteristics of SJS/TEN between the patients with and without the HLA-B*15:02 allele. Notably, further studies using larger samples are required to confirm these conclusions.
ObjectivesTo evaluate the efficacy and safety of lacosamide (200mg/d and 400mg/d)when added to 1 to 3 antiepileptic drugs (AEDs) in adults with uncontrolled partial-onset seizures. MethodsDuring this multicenter, double-blind, placebo-controlled trial, patients were randomized to placebo or lacosamide 200 or 400mg/day after an 8-week baseline period. Lacosamide was titrated in weekly increments to target dose over 4 weeks and maintained for 12 weeks followed by 12 weeks for withdrawal. The reductions of seizure frequence during maintain period and proportion of ≥50% reduction of seizures frequence were analysed. Besides,adverse effects were also recorded. ResultsFive hundred fourty patients were randomized, 515 patients completed the trial (Full analysis set, FAS), including 394 were per-protocol set (PPS). The reduction of seizure frequence during maintain period every 4 weeks among 200mg/d,400mg/d group and placebo group were 26.35%,40.12%,21.69%(P=0.000 5) and 25.61%,46.86%,23.06%(P<0.000 1), respectively in FAS and PPS. The proportion of ≥50% reduction of seizures frequence among three groups were 29.82%,38.15%,22.49%(P=0.006 8) and 27.94%,42.37%,22.86%(P=0.002 3), respectively in FAS and PPS. The incidences of adverse events were 5.84%, 36.11%, 19.55% among three groups. Compared with each other, there was statistic significance between 400mg/d and placebo groups. ConclusionIn this trial, adjunctive lacosamide significantly reduced seizure frequency in patients with uncontrolled partial-onset seizures. Along with favorable pharmacokinetic and tolerability profiles, these results support further development of lacosamide as an AED.