Authors :
Rui Loureiro, Bial – Portela & Cª, S.A.; João Chaves - Bial – Portela & Cª, S.A., Coronado, Portugal; Joana Moreira - Bial – Portela & Cª, S.A., Coronado, Portugal; Ana Pereira - Bial – Portela & Cª, S.A.; Fábio Ikedo - Bial – Portela & Cª, S.A.;;
Rationale:
Theoretically, antiepileptic drug (AED) combinations with the same mechanism of action may be less adequate than targeting different mechanisms of action. It remains unclear whether AEDs with different mechanisms of action are more likely to interact synergistically than AEDs with similar mechanisms.1,2
The aim of this exploratory post hoc analysis was to evaluate safety and tolerability of eslicarbazepine acetate (ESL) as adjuvant therapy to one concomitant AED.
Method:
Data was pooled from four Phase III, randomized, double-blind, placebo-controlled trials (BIA-2093-301, -302, -303, -304) that evaluated ESL efficacy and safety as add-on treatment in adult patients with focal-onset seizures (FOS).
Safety and tolerability were assessed by the incidence of treatment emergent adverse events (TEAE) at least possibly related and discontinuation due to TEAE, in patients treated with one AED (any) and according to subgroups of patients treated with one selective concomitant AED: carbamazepine (CBZ), lamotrigine (LTG) or levetiracetam (LEV).
Results:
The safety population included 1699 patients and the ITT included 1480 patients. At baseline, the mean age for the ITT was approximately 37 years. Two thirds of patients were diagnosed with epilepsy when < 18 years and about half of the patients have had epilepsy for more than 20 years. At baseline, 455 patients were taking one AED (CBZ: 209, 73.6%; LTG: 44, 15.5% and LEV: 31, 10.9%).
In patients treated with ESL and one concomitant AED, the most frequent TEAE at least possible related were dizziness (15.2%), somnolence (11.9%) and nausea (7.6%). The most frequent TEAE leading to discontinuation were dizziness (4.9%), nausea/vomiting (2.4%) and somnolence (2.1%). A dose effect response was observed (Table 1).
ESL as add-on to treatment regimens containing LEV had the lowest frequency of TEAE. Only one TEAE of dizziness and somnolence (4.3%), 2 TEAE (8.7%) of headache (8.7%) and no other TEAE was reported. ESL as add-on to treatment regimens containing LEV had the lowest frequency of discontinuation due to TEAE: dizziness nausea vomiting and somnolence (0%). ESL as add-on to treatment regimens containing CBZ had the highest frequency of TEAE and discontinuation due to TEAE (Table 2).
Conclusion:
In this exploratory post hoc analysis, ESL was safe and well tolerated as add-on treatment to one AED in adult patients with FOS. ESL as add-on to treatment regimens containing LEV appeared to be associated with lower incidences of some TEAEs. These findings are consistent with published literature and support the use of ESL as adjunctive therapy to one baseline AED.
Funding:
:Bial Portela e C. SA, Coronado (S. Romão e S. Mamede), Maia, Portugal
FIGURES
Figure 1