Clinical practice data demonstrates clinical effectiveness and tolerability of Zebinix� (eslicarbazepine acetate) as adjunctive therapy in epilepsy patients with psychiatric comorbidities
Bial and Eisai today announce clinical practice data from the Euro-Esli study demonstrating clinical effectiveness of eslicarbazepine acetate, and that it is generally well tolerated as an adjunctive therapy in focal epilepsy patients with psychiatric comorbidities, including intellectual disability, compared with people with no psychiatric comorbidities.1 The data, which add to the body of evidence on eslicarbazepine acetate as adjunctive therapy from Phase III studies2,3,4,5 were published in Journal of the Neurological Sciences.1
Psychiatric comorbidities, including intellectual disability and depression, are common for adults who have epilepsy.6,7 Prevalence of psychiatric comorbidities may be twofold higher in adult patients with epilepsy compared to the general public, and up to a quarter of people diagnosed with epilepsy are estimated to have an intellectual disability.6,7 Psychiatric comorbidities can exacerbate the effects and increase the impact of epilepsy.8 Furthermore, antiepileptic treatments can interfere with treatments for the psychiatric comorbidities, and thus adversely affect these psychiatric conditions.9,10 There are many considerations for treating this patient population, thereby complicating treatment choice.10
“The comorbidities of epilepsy represent a substantial burden for people with epilepsy. This data provides a significant insight into how eslicarbazepine acetate performs in a routine medical setting for these patients and the results are very encouraging, demonstrating eslicarbazepine acetate's efficacy and tolerability as an adjunctive therapy in this sub-set of patients,” comments Dr Colin Doherty, Consultant Neurologist, St James’s Hospital, Dublin, Ireland, and lead author of the Euro-Esli study.
This newly published data includes patient populations that are sometimes excluded from clinical trials, including those with psychiatric comorbidities, specific comorbidities of intellectual disability, or depression.1,11 Adverse events reported during this sub-cut of the Euro-Esli study are consistent with eslicarbazepine acetate’s safety profile established in Phase III studies.1,2,3,4,5 Adverse events with eslicarbazepine acetate treatment were reported by 43.1% of people with psychiatric comorbidities (n=122/283) and 45.8% of people with intellectual disability (n=49/107). The most common adverse events were dizziness (11.4%; n=31/272), somnolence (8.8%; n=24/272) and fatigue (8.1%; n=22/272) for people with psychiatric comorbidities; and somnolence (10.1%; n=10/99), dizziness (7.1%; n=7/99) and fatigue (6.1%; n=6/99) for people with intellectual disability.1
Psychiatric comorbidities
Treatment with eslicarbazepine acetate in people with psychiatric comorbidities showed a responder rate of 83.1% (n=128/154) (defined by ≥50% seizure frequency reduction from baseline) at 12 months, compared with 82.5% (n=326/395) of people without psychiatric comorbidities (p=0.871). Seizure freedom was achieved by 51.3% of people with psychiatric comorbidities (n=79/154) (defined as no seizures since at least the prior visit) at 12 months with eslicarbazepine acetate treatment, compared with 51.4% (n=203/395) of people in the no psychiatric comorbidities group (p=0.984).1
Adverse events were reported by 43.1% of people with psychiatric comorbidities (n=122/283) compared to 30.5% of people without psychiatric comorbidities (n=261/855; p<0.001). Psychiatric adverse events were reported by 3.7% of people with psychiatric comorbidities (n=10/272) compared to 1.8% of people without psychiatric comorbidities (n=15/822; p=0.076). Discontinuation of treatment with eslicarbazepine acetate due to adverse events occurred in 17.2% of people with psychiatric comorbidities (n=45/262) compared with 11.6% of people without psychiatric comorbidities (n=94/811; p=0.019).1
Intellectual disability
Treatment with eslicarbazepine acetate in people with intellectual disability showed a responder rate of 60.3% (n=35/58) at 12 months, compared with 76.6% (n=222/290) of people without intellectual disability (p=0.010). Seizure freedom was achieved by 22.4% of people with intellectual disability (n=13/58) at 12 months with eslicarbazepine acetate treatment, compared with 43.1% (n=125/290) of people without intellectual disability (p=0.003).1
Adverse events were reported by 45.8% of people with intellectual disability (n=49/107) compared to 32.6% of people without intellectual disability (n=275/844; p=0.007). Cognitive adverse events were reported by 4.0% of people with intellectual disability (n=4/99) compared to 3.8% of people without intellectual disability (n=31/809; p=0.919). Discontinuation of treatment with eslicarbazepine acetate due to adverse events occurred in 22.4% of people with intellectual disability (n=22/98) compared with 14.8% of people without intellectual disability (n=117/789; p=0.050).1
Depression
Treatment with eslicarbazepine acetate in people with depression showed a responder rate of 81.0% (n=51/63) at 12 months, compared with 82.9% (n=402/485) of people without depression (p=0.703). Seizure freedom was achieved by 46.0% (n=29/63) of people with depression at 12 months with eslicarbazepine acetate treatment, compared with 52.0% (n=252/485) of people without depression (p=0.376).1,12
Adverse events were reported by 42.6% of people with depression (n=60/141) compared to 32.4% of people without depression (n=322/993; p=0.017). Psychiatric adverse events were reported by 4.4% of people with depression (n=6/136) compared to 2.0% of people without depression (n=19/955; p=0.074). Discontinuation of treatment with eslicarbazepine acetate due to adverse events occurred in 18.5% of people with depression (n=24/130) compared with 12.1% of people without depression (n=114/939; p=0.044).1
The Euro-Esli study presents a clinical practice data set of eslicarbazepine acetate with 2,058 patients included.13 The Euro-Esli study has a broad set of inclusion/exclusion criteria, allowing for the representation of people with conditions sometimes excluded from clinical trials.13,14 The Euro-Esli study includes a diverse patient population with challenging comorbidities, and provides robust evidence to support clinical practice and treatment decisions.13,14
Eslicarbazepine acetate is approved in the European Union (EU) as adjunctive therapy in adults, adolescents and children aged above 6 years, with partial-onset seizures with or without secondary generalisation.15 Eslicarbazepine acetate has also been approved in the EU as monotherapy in the treatment of partial-onset seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy in 2017.15
References:
1. Doherty C, et al. (2019) Eslicarbazepine acetate in epilepsy patients with psychiatric comorbidities and intellectual disability: Clinical practice findings from the Euro-Esli study. Journal of the Neurological Sciences. DOI: https://doi.org/10.1016/j.jns.2019.04.040.
2. Elger C, et al. (2009) Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial onset seizures: A randomised, double-blind, placebo-controlled, parallel-group phase III study. Epilepsia. 50:454-63.
3 Ben-Menachem E, et al. (2010) Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy. Epilepsy Research. 89(2-3):278-85.
4. Gil-Nagel A, et al. (2009) Efficacy and safety of 800 and 1200 mg eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures. Acta Neurologica Scandinavica. 120:281-87.
5. Sperling M, et al. (2015) Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial. Epilepsia. 56(2):244-53.
6. Gaitatzis A, et al. (2004) The epidemiology of the comorbidity of epilepsy in the general population. Epilepsia. 45(12):1613-22.
7. Lhatoo S, et al. (2001) The epidemiology of epilepsy and learning disability. Epilepsia. 42 Suppl 1:6-9.
8. Gilliam F, et al. (2003) Psychiatric comorbidity, health, and function in epilepsy. Epilepsy Behav. 4 Suppl 4:S26-30.
9. Kanner A. (2016) Management of psychiatric and neurological comorbidities in epilepsy. Nat Rev Neurol. 12(2):106-16
10. Mula M (2013) Treatment issues for psychiatric comorbidities of epilepsy. Clin. Pract. 10(3):293-299.
11. Tlusta E, et al. (2008) Clinical relevance of patients with epilepsy included in clinical trials. Epilepsia. 49, 1479-80.
12. Doherty C, et al. (2019) Eslicarbazepine acetate in epilepsy patients with psychiatric comorbidities and intellectual disability: Clinical practice findings from the Euro-Esli study. Supplementary Data. Journal of the Neurological Sciences. DOI: https://doi.org/10.1016/j.jns.2019.04.040.
13. Villanueva V, et al. (2017) Euro-Esli: a European audit of real-world use of eslicarbazepine acetate as a treatment for partial-onset seizures. Journal of Neurology. 264(11):2232-48.
14. Finnegan M, et al. (2017) Rethinking vulnerable groups in clinical research. Irish Journal of Psychological Medicine. doi: 10.1017/ipm.2017.73.
15. European Medicines Agency (2019) Zebinix® (eslicarbazepine acetate) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/zebinix-epar-product-information_en.pdf. Last accessed June 2019.
16. Hebeisen S, et al. (2015) Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: A comparison with carbamazepine, oxcarbazepine and lacosamide. Neuropharmacology. 89:122-35.
17. Jó?wiak S, et al. (2018) Effects of adjunctive eslicarbazepine acetate on neurocognitive functioning in children with refractory focal-onset seizures. Epilepsy & Behavior. 81:1-11.
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