Valproate, Regardless of Add-On Levetiracetam, Decreases Inflammatory Biomarker CCL2


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.

Rajarshi Kar, MBBS

Rajarshi Kar, MBBS

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.”

Labh R, Gupta R, Narang M, Halder S, Kar R. Effect of valproate and add-on levetiracetam on inflammatory biomarkers in children with epilepsy. Epilepsy Behav. Published online October 27, 2021. doi:10.1016/j.yebeh.2021.108358.
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