Clobazam Combo Tx Beneficial in Lennox−Gastaut Syndrome

The median reductions in average weekly drop seizure rate from baseline was assessed to evaluate the efficacy of CLB vs. placebo
The median reductions in average weekly drop seizure rate from baseline was assessed to evaluate the efficacy of CLB vs. placebo

According to results of a post hoc analysis presented at the AES Annual Meeting 2017, patients with Lennox-Gastaut syndrome (LGS) experienced improved seizure control and reduced seizure rates when clobazam (CLB) was added to therapy with other commonly prescribed antiepileptic drugs (AEDs).

To determine the efficacy of CLB in combination with other AEDs, data from the ‘CONTAIN' study was analyzed. The study was randomized, double-blind, and placebo-controlled. During the study, patients receiving 1 to 3 AEDs were randomized to receive placebo (PBO), low dose CLB (0.25mg/kg [max: 10mg/day]), medium dose CLB (0.5mg/kg [max: 20mg/day)], or high dose CLB (1.0mg/kg [max: 40mg/day]). The patients received the study medication over a 3-week titration period followed by a 12-week maintenance period.

The median percent reductions in average weekly drop seizure rate from baseline was assessed post hoc, to evaluate the polytherapy efficacy of CLB vs. placebo, in those patients receiving the most common concomitant AEDs (valproic acid, VPA; lamotrigine, LTG; levetiracetam, LEV; topiramate, TPM). Additionally, the seizure response in each treatment group, defined as a reduction of ≥50% in the average weekly drop seizures, was measured from baseline to the maintenance period.

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At baseline, the patients included in the study were an average (SD) age of 12.4 (9.0) years old with an average (SD) 86.6 (161.5) drop seizures/week. 35.3% of the patients were receiving concomitant VPA, 32.8% were receiving LTG, 31.5% were receiving LEV, and 30.3% were receiving TPM.

The authors reported, “Patients receiving concomitant VPA or TPM experienced significantly greater median reductions in average weekly drop seizures with add-on medium (VPA: 71.2%, TPM: 71.2%) or high (VPA: 81.8% and TPM: 87.3%) dosage CLB compared with PBO/VPA (31.6%, P<0.05) and PBO/TPM (47.6%, P<0.05).”

Results also showed that a significantly greater reduction in seizures was observed in patients receiving high-dose CLB/LTG compared to those receiving PBO/LTG (87.3% vs 46.2%, respectively; P<0.05). Similarly, a larger seizure reduction was seen in patients receiving low-dose CLB/LEV, medium-dose CLB/LEV, and high-dose CLB/LEV compared to patients receiving PBO/LEV (63.7%, 51.2%, 73.8%, and 33.6%, respectively; P<0.05).

Nearly double the patients receiving CLB/TPM and CLB/LEV were ≥50% responders compared to patients receiving PBO/TPM or PBO/LEV.

According to findings of this post hoc analysis, for patients with LGS, seizure control is improved when medium- and high-dose CLB is combined with VPA, LTG, LEV, or TPM.

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Reference

Chung S S. Combination AED treatment with clobazam in patients with lennox-gastaut syndrome: Post-hoc analyses of the contain study. Presented at AES annual meeting in Washington, DC. Abstract 2.429.