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Fewer Lifetime AED Use Decreases Odds of Discontinuing Brivaracetam for Focal Seizures

Data suggest that treatment-emergent adverse events with adjunctive brivaracetam increased in incidence by number of lifetime AEDs.

Data from a recent post-hoc analysis of the randomized, double-blind, placebo-controlled (NCT01261325) and open-label extension (NCT01339559) trials of adjunctive brivaracetam (BRV) in patients ≥16 years with focal seizures has shown that patients with fewer numbers of lifetime anti-epileptic drugs (AEDs) were less likely to discontinue BRV due to lack of efficacy or treatment-emergent adverse events (TEAEs).

“One lesson I would draw from the study is that you really do want to try to get to patients early on and be as aggressive with your treatment choice as you can. You don't want to have a situation where somebody has failed three medications, and the physician gives up and says, ‘Oh, well, the patient's got 4 seizures a month, it could be worse, it could be 20. And there's nothing that can be done. Here is a prescription for the 3 medications.’ And they do this year after year for 10 years; that's 10 years of time lost and 10 years of disease progression,” study presenter Pavel Klein, MD, director, Mid-Atlantic Epilepsy and Sleep Center told NeurologyLive.

“If you can get to that patient earlier, and instead of giving them the same 3 medication prescriptions for next 10 years, try to find new treatments, whether it be medications, surgical treatment, or dietary treatment, we have to keep looking for new treatments and there's a reasonable chance that some treatment could make a big difference,” he added.

Klein and colleagues presented their results at the American Epilepsy Society (AES) Virtual Meeting, December 4–8, 2020. Klein and colleagues analyzed data from 740 patients randomized to 100 or 200 mg/day of BRV or placebo for a median treatment duration of 973.5 days. Out of these patients, 102 (52.9%) had been exposed to 1–2 lifetime AEDs, 154 (45.5%) had been exposed to 3–4, 156 (52.6%) had been exposed to 5–6, and 328 (39.9%) had been exposed to ≥7 lifetime AEDs.

WATCH NOW: Pavel Klein, MD: Finding the Right AEDs for Patients With Epilepsy

The main reason for BRV discontinuation in patients with 1–4 lifetime AEDs was consent withdrawal. In those with ≥5 lifetime AEDs, the main reason was lack of efficacy. The Kaplan-Meier estimated retention of BRV was 83.2% at 12 months and 63% at 36 months in patients with 1–2 lifetime AEDs, 71.3% at 12 months and 56% at 36 months in patients with 3–4, 65.9% at 12 months and 59.3% at 36 months in patients with 5–6, and 65.9% at 12 months and 44.1% at 36 months in patients with ≥7 lifetime AEDs.

Patients with 1–2 lifetime AEDs had a median percent reduction from baseline in focal seizure frequency per 28 days of 76.3%. Patients with 3–4 had a 56.7% median reduction, patients with 5–6 had a 50.9% median reduction, and patients with ≥7 lifetime AEDs had a median seizure reduction of 39.6%. The 50% responder rates were 66.7% in patients with 1–2 lifetime AEDs, 56.9% in patients with 3–4, 51.9% in patients with 5–6, and 39.8 in patients with ≥7 lifetime AEDs. The 75% responder rates were 51.0% in patients with 1–2 lifetime AEDs, 34.0% in patients with 3–4, 26.3% in patients with 5–6, and 19.6% in patients with ≥7 lifetime AEDs.

Continuous seizure-freedom rates for ≥1 year at any time during treatment was 35.3% in patients with 1–2 lifetime AEDs, 15.7% in patients with 3–4, 12.2% in patients with 5–6, and 6.1% in patients with ≥7 lifetime AEDs. Median percent reduction in focal seizure frequency, and 50% and 75% responder rates, were sustained over time in all numbers of lifetime AEDs in patients completing at least 48, 96, or 144 weeks.

The incidence of TEAEs was 86.3% in patients with 1–2 lifetime AEDs, 84.4% in those with 3–4, 90.4% in those with 5–6, and 90.5% in those with ≥7 lifetime AEDs. Discontinuations due to TEAEs occurred in 7.8% of patients with 1–2 lifetime AEDs, 10.4% in those with 3–4, 14.1% in those with 5–6 and 20.1% of patients with ≥7.

"Brivaracetam’s effective and it has a favorable safety profile. Unlike most AEDs, because the side effect profile is so relatively benign, you don't have to titrate the doses, you can start at the target dose. In general, we have to keep the research going... and don't give up on any patient. Be there for your patients,” Klein said.

For more coverage of AES 2020, click here.

Klein P, Dimova S, Brandt C, Laloyaux C, Nondonfaz X, Elmoufti S. Long-term retention, efficacy and tolerability of adjunctive brivaracetam by number of lifetime antiepileptic drugs in adults with focal seizures: A post hoc analysis. Presented at AES 2020 Annual Meeting; December 4–8, 2020. Abstract 134.