Obesity and overweight as CAE comorbidities and differential drug response modifiers.

Abstract

This study examined whether overweight and obesity are pretreatment comorbidities and predictors of short-term drug response in newly diagnosed untreated childhood absence epilepsy (CAE). We also examined whether dietary intake accounts for observed pretreatment body mass index (BMI) distribution. Pretreatment height and weight were available for 445 of 446 participants in the NIH-funded CAE comparative effectiveness trial (NCT00088452). Twenty-four-hour dietary recalls were collected. Calculated BMI and dietary intake were standardized for age, sex, and race/ethnicity and compared to age-matched US population from the National Health and Nutrition Examination Survey (NHANES). Logistic regression models tested BMI as a predictor of treatment response. Pharmacokinetic variables were explored as contributors to differential drug response. After standardizing for demographic differences, children with CAE were more likely to be overweight (19.3% vs 13.8%; p < 0.001) or obese (14.5% vs 11.5%; p < 0.001) than NHANES controls. The combined prevalence of overweight and obesity was 33.8% in the CAE cohort and 25.3% among controls (p < 0.001). Mean daily energy intake (difference -79.5 kcal/day, p = 0.04) and daily carbohydrate intake (difference -10.7 g/day, p = 0.04) were lower in the CAE group than in NHANES controls. With increasing baseline BMI z score, the efficacy and effectiveness of ethosuximide and valproic acid over lamotrigine became more pronounced, despite no significant differences in drug exposure and trough levels. Overweight and obesity are more prevalent in children with newly diagnosed CAE than in age-matched peers, despite lower caloric and carbohydrate intake. Baseline BMI may also predict differential drug response, which cannot be attributed to pharmacokinetic differences.