Efficacy of Brivaracetam (BRV) as Adjunctive Therapy in Partial-Onset (Focal) Seizures Among Patients with Prior Levetiracetam (LEV), Carbamazepine (CBZ), Lamotrigine (LTG), or Topiramate (TPM) Exposure (P2.027)

OBJECTIVE: To explore the efficacy of adjunctive BRV in adults ≥16 years receiving 1-2 antiepileptic drugs (AEDs), with prior LEV, CBZ, LTG or TPM exposure compared with LEV-, CBZ-, LTG-, or TPM-naive patients. BACKGROUND: Pooled analysis of Phase III studies (NCT00490035, NCT00464269, NCT01261325) showed BRV has statistically significant efficacy over placebo in patients with prior LEV exposure, but numerically greater efficacy in LEV-naive patients. DESIGN/METHODS: The pooled Phase III population (N=1160) comprised patients randomized to BRV 50, 100, or 200mg/day (without titration) or placebo, excluding those taking concomitant LEV (not permitted in NCT01261325). Patients were categorized post hoc by CBZ, LEV, LTG and TPM status: naive or prior exposure (discontinued >90 days before enrolment). Demographics and ≥50[percnt] responder rates were evaluated in patients with prior AED exposure versus corresponding AED-naive subgroups. RESULTS: More patients with prior LEV exposure had ≥5 prior AEDs (356/531, 67.0[percnt]) versus their LEV-naive counterparts (78/629, 12.4[percnt]). This was also seen in prior versus naive CBZ (242/388, 62.4[percnt] versus 52/296, 17.6[percnt]), LTG (224/311, 72.0[percnt] versus 84/553, 15.2[percnt]) and TPM (271/380, 71.3[percnt] versus 99/612, 16.2[percnt]) patients. Across treatment groups, prior LEV patients had higher baseline median weekly seizure frequency than LEV-naive patients (8.7-11.8 versus 7.0-9.3, respectively), with the same pattern seen for CBZ, LTG, and TPM. The ≥50[percnt] responder rates for LEV-naive patients (37.2[percnt] 50mg/day, 48.3[percnt] 100mg/day, 45.2[percnt] 200mg/day versus 22.5[percnt] placebo) were consistently higher than in the corresponding prior LEV treatment groups (27.1[percnt], 29.7[percnt], 31.3[percnt] versus 17.8[percnt], respectively). CBZ, LTG, and TPM groups had the same trend of higher efficacy in AED-naive patients. CONCLUSIONS: Reduced efficacy of BRV in the prior LEV group was also reflected in the prior CBZ, LTG, and TPM groups. Demographic and prior AED exposure data suggest these patients may have more refractory epilepsy. Study supported by UCB Pharma.