Cenobamate Shows High Retention, Increased Risk of Depression in MS, DAPT Therapy Benefits Moderate Ischemic Stroke

This week Neurology News Network covered the recently published results of cenobamate's high retention rate in adults with treatment-resistent focal epilepsy, the increased risk for patients with MS dependent on DMT use, and the exploratory analysis of the THALES trial utilizing dual antiplatelet therapy in moderate ischemic stroke.

Welcome to this special edition of Neurology News Network. I’m Marco Meglio. Please excuse our appearance this week as a majority of the US workforce, including the NeurologyLive team, moves to working remote as we come together to help reduce the spread of the novel coronavirus.

Newly published data from an open-label extension (OLE) of the 12-week C013 study showed significant long-term retention of adjunctive cenobamate for up to 7.8 years in adults with treatment-resistant focal epilepsy taking 1 to 3 antiseizure medications. The OLE of the original multi-center, double-blind, placebo controlled study included 149 adults with uncontrolled focal seizures who had median treatment duration of 6.25 years with cenobamate. As of the data cut-off in July 2019, 57% (n = 85) of patients remained in the OLE (median treatment duration, 6.8 years.The median modal daily cenobamate dose was 200 mg. Based on a Kaplan-Meier analysis, the probability of continuing treatment was 73% after 1 year, 67% after 2 years, 63% after 3 years, 61% after 4 years, 60% after 5 years, and 59% after 6 years. Among the patients who continued treatment at 1 year (n = 107), the probability of continuing treatment was 92% after 2 years, 87% after 3 years, 83% after 4 years, and 82% after 5 years.

A nationwide cohort study in Sweden found patients with multiple sclerosis (MS) face subsequent risk for depression, depending on the disease-modifying therapies (DMTs) employed in their treatment regimen. The use of antidepressants or depression diagnosis showed limited associations with discontinuation of DMTs and MS relapse. A total of 3803 patients with relapsing-remitting MS (RRMS) were included in the study, which spanned 8 years and drew data from the Swedish MS Registry. Compared to those treated with interferons, investigators found a lower risk for depression diagnosis or initiating antidepressants in patients taking rituximab. Patients with depression more often discontinued the use of interferon treatment, compared to those not diagnosed with depression.

An exploratory analysis of the THALES clinical trial showed that patients with moderate ischemic stroke consistently benefitted from a dual antiplatelet therapy, or DAPT, of ticagrelor (Brilinta; AstraZeneca) plus aspirin compared to patients with less severe ischemic stroke, with no increased safety concerns. Ticagrelor previously received FDA approval in November 2020 to reduce the risk of stroke in patients with acute ischemic stroke (AIS) or high-risk transient ischemic attack (TIA). The THALES trial was the basis for the approval, in which approximately 30% of the patient population had National Institutes of Health Stroke Scale (NIHSS) scores between 4 to 5.The primary outcome, time to stroke or death within 30 days, was observed in 7.6% of patients with moderate stroke for those in the ticagrelor group and 9.1% for those in the placebo group. Additionally, the primary outcome event rate in patients with less severe stroke was 4.7% for those in the ticagrelor group and 5.7% for those in the placebo group.

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