In addition to changes in CCL2 levels, anxiety and health-related quality of life were both significantly increased in both the valproate and add-on levetiracetam groups.
Data from an open-label, prospective, observational study of children with generalized or focal seizures showed that treatment with valproate and levetiracetam led to a decrease in serum levels of C–C motif ligand 2 (CCL2) and no change in interleukin-1 beta (IL-1ß).
To learn more about the role inflammatory markers play in epilepsy, senior author Rajarshi Kar, MBBS, assistant professor of neurology, University of Delhi, and colleagues examined a cohort of 40 patients on valproate and 40 patients on valproate with add-on levetiracetam. In addition to evaluating changes in serum CCL2 and IL-1ß levels, investigators also measured anxiety and health-related quality of life (HRQol), using Spence Children Anxiety Scale short version (SCAS-S) and QOLCE-16 scales, respectively.
At the conclusion of the 16-week observation period, serum CCL2 levels significantly decreased from 327.95 pg/mL (±59.07) to 207.02 pg/mL (±41.50) in the valproate-only group (P <.001). For the add-on group, serum CCL2 levels at the start of treatment were 420.65 pg/mL (±83.72), which significantly decreased to 250.06 pg/mL (±46.05) at 16 weeks. Patients in the add-on group not only had significantly higher CCL2 levels at baseline than the valproate alone group but demonstrated a significantly greater decrease in serum CCL2 levels (P <.001).
The study authors concluded that the "anti-inflammatory property of valproate and levetiracetam might underlie their antiepileptic effect and CCL2 could be a potential marker of drug efficacy in epilepsy."
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Neither treatment group experienced significant changes in serum IL-1ß levels at the 16-week mark. Those in the valproate group had levels change from 29.03 (±6.62) pg/ml at the beginning of treatment to 29.88 (±5.47) pg/ml at the end of the study period (P = .087). Similarly, those in the add-on therapy group had serum IL-1ß levels of 42.75 (±8.74) pg/ml at the end of the 16-week period, compared to 38.48 (±9.60) mg/ml at baseline.
Anxiety levels using SCAS-S, validated in ages 7 to 12 years, were recorded at weeks 4, 8, 12, and 16 for those in both groups (valproate: n = 32; valproate add-on: n = 30). Investigators identified a significant decrease in SCAS-S score from an initial score of 61.41 (±9.68) in the valproate group to a posttreatment score of 47.69 (±6.43) and from an initial score 67.06 (±10.02) in the add-on levetiracetam group to a posttreatment score of 46.13 (±6.55).
The QOLCE-16 scale, which is validated for ages 4-12, was used to assess the effect of these drugs on HRQoL in epilepsy at the same time periods as SCAS-S. Results showed a significant effect with treatment in both drug groups, with increases in QOLCE-16 scores from 31.36 (±5.63) to 49.46 (±8.6) in the valproate group and increases from 29.25 (±6.19) to 49.96 (±8.77) in the add-on levetiracetam group.
Anorexia (40%), nausea-vomiting (25%), and sedation (20%) were the most reported adverse drug reactions in the valproate group. Sedation (30%), nausea-vomiting (30%), and anorexia (30%) were among the most common adverse drug reactions in the add-on levetiracetam group, followed by weakness (20%). Those in this group also experienced weight gain (7.5%) and alopecia (5%). Notably, neither treatment group reported any serious adverse events.
After concluding that CCL2 could serve as a useful biomarker for underlying disease process and therapeutic response in epilepsy, investigators also wrote that “identification of such biomarkers for epilepsy may provide tailor-made drug therapies to pediatric patients minimizing the adverse effects of antiseizure medication and achieving their maximum therapeutic benefits.”