At the 35^th Annual Scientific Meeting of the Hong Kong Neurological Society, Professor Steve Chung shared his experience in choosing the appropriate treatment plan for patients with epilepsy. He urged physicians to consider treatment from a holistic point of view, incorporating personalized medicine, especially for patients suffering from cognitive comorbidities.

Difficulties and recommendations on initiating epilepsy treatment

In the presentation, Prof. Chung highlighted that most patients with newly-diagnosed epilepsy have a constant course of disease, which could be predicted early on. However, up to 66% of patients with epilepsy are not adherent to their medication. According to the World Health Organization (WHO), non-adherence is commonly caused by forgetfulness, refusal to take medication and avoidance of adverse effects (AEs) of the medication.¹

Therefore, clinicians are recommended to personalize antiepileptic medication (AEM) after the first seizure based on individualized assessments by determining the risk of recurrence against the AEs of AEM, in addition to considering the preferences of patients.²

Clinical decision-making for AEM

Initial treatment is vital to optimizing the patient’s overall treatment plan, and that highly personalized epilepsy treatment should be administered at the very beginning. A study showed that up to 49.5% of patients with newly-diagnosed epilepsy had remained seizure-free for over 1 year on the first prescribed AEM, while 31.7% of patients remained refractory after the fourth line of treatment.³ Prof. Chung mentioned that this study indicated the significance of choosing a medication that can address most issues, then adhering to it as a long-term medication for patients. He then outlined the trifecta, including clinical evidence, external factors and patient/physician factors, that contributes to the clinical decision-making which can be summarized into 4 domains, including seizure types and patient characteristics, drug efficacy and safety, comorbid conditions and concurrent medications, and lastly, patient preference and cost.⁴

Brivaracetam in patients with epilepsy with comorbid-mood disorder

Apart from initial diagnosis and patient preferences, treatment selection should also be based on patient characteristics.³ Mood disorder is the most common comorbidity with epilepsy.⁵ Given that patient may have comorbid headaches, depression and anxiety, it is necessary to take into consideration these factors when it comes to selecting the appropriate treatment.⁵ Prof. Chung identified parameters like psychiatric AEs and the incidence of suicide ideation as essential to consider in the course of his epilepsy management for patients.

One of the stand-out therapies that can satisfy the above criteria in epilepsy treatment is brivaracetam. As a new-generation AEM, brivaracetam is found to have relative improvement in terms of higher potency and selectivity when compare to levetiracetam.⁶ In a pooled analysis of clinical trials, brivaracetam did not significantly influence the rates of irritability, insomnia, anxiety, and depression compared with placebo (figure 1).⁷ Another pooled analysis also showed that brivaracetam did not increase the incidence of suicidal ideation compared with placebo (figure 2).⁸

DDIs of AEM

Prof. Chung highlighted that the final consideration is drug-drug interactions (DDIs). AEMs are notorious for their DDIs, not only with other medications, but within the AEM class as well.¹⁰ Even new drugs like eslicarbazepine still retain a lot of these interactions.10 Fortunately, brivaracetam does not interact with a lot of other AEMs (table 1).⁸

Conclusion

To conclude, brivaracetam, as an AEM, has shown promising efficacy in patients with epilepsy in terms of higher potency and selectivity compared to levetiracetam.⁶ When compared with placebo, similar rates of irritability, insomnia, anxiety, depression and suicidal ideation were observed with brivaracetam.⁷ Brivaracetam also has a lower risk of DDIs than other AEMs.⁸ Prof. Chung reminded that clinical decisions should be made upon considering a combination of clinical evidence, patient/physician factors, and external factors. It is also essential to consider the characteristics of patients so as to work out an optimal epilepsy management plan.

^{_{NAME OF THE MEDICINAL PRODUCT BRIVIACT (brivaracetam) Active Ingredient: Brivaracetam - Tablets: 25, 50 and 100mg. Oral Solution: 10mg per ml. Injection/Infusion: 10mg per ml. Indications: Adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalisation in adult and adolescent patients from 16 years of age with epilepsy. Dosage and Administration: Starting dose of 50 or 100mg/day, adjusting up to 200mg/day. All daily doses to be given in two equally divided doses, morning and evening with or without food. All dose adjustments based on physician’s assessment, patient response and tolerance. Swallow tablets whole with liquid. Oral solution may be diluted in water or juice shortly before administration orally, via nasogastric or gastrostomy tube. Injection/ infusion may be given as an intravenous bolus or diluted in a compatible solution and administered as a 15-minute intravenous infusion. Injection/ infusion is not recommended in acute conditions, such as status epilepticus. Renal impairment: No dose adjustment is needed but not recommended in end-stage renal disease patients undergoing dialysis due to lack of data. Hepatic impairment: Exposure is increased in chronic liver disease - see full prescribing information for dose guidance. Elderly: Limited experience but no dose adjustment needed. Discontinuation: Withdraw gradually – see full prescribing information for dose guidance. Contraindications: Hypersensitivity to brivaracetam, other pyrrolidone derivatives or to any of the excipients listed in the full prescribing information. Warnings: Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic drugs (AEDs). Patients should be monitored and appropriate treatment considered. Dose adjustment recommended in hepatic impairment. Tablets not to be taken by patients with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.Interactions: Brivaracetam plasma concentrations may increase with CYP2C19 strong inhibitors (risk of a clinically relevant CYP2C19 mediated interaction considered to be low). Coadministration of cannabidiol may increase the plasma exposure of brivaracetam (Tabs). Brivaracetam plasma concentrations decreased with strong enzyme inducing AEDs but no dose adjustment is required. Caution and consider adjusting the brivaracetam dose in patients starting or ending treatment with rifampicin or St John’s Wort, strong inducers of CYP2C19. Brivaracetam may increase plasma concentrations of medicinal products metabolised by CYP2C19 or transported by OAT3 and decrease plasma concentrations of medicinal products metabolised by CYP2B6. Potential interactions between brivaracetam and other AEDs were investigated, please refer to the full prescribing information section 4.5 for full details. Concomitant alcohol intake is not recommended. Pregnancy and lactation: Discuss family planning and contraception with women of childbearing potential taking brivaracetam. As a precaution, should not be used during pregnancy unless clinically necessary. It is unknown whether brivaracetam is excreted in human breast milk so a clinical decision needs to be made as to whether to discontinue either breastfeeding or brivaracetam. Driving and operate machinery: Brivaracetam has minor or moderate influence on the ability to drive and use machines (may include somnolence, dizziness, and other central nervous system related symptoms). Patients should be advised not to drive or to operate other potentially hazardous machines until familiar with the effects of brivaracetam. Adverse Effects: Very Common (≥1/10): Dizziness, somnolence. Common (≥1/100 - <1/10): Influenza, decreased appetite, depression, anxiety, insomnia, irritability, convulsion, vertigo, upper respiratory tract infections, cough, nausea, vomiting, constipation, fatigue. Uncommon (≥1/1000 - <1/100) neutropenia, type 1 hypersensitivity, suicidal ideation, psychotic disorder, aggression, agitation. See full prescribing information for further details. Pharmaceutical Precautions: Oral solution: Use within 5 months of opening. Injection/Infusion: Use immediately after dilution.}}

^{_{Please refer to the full prescribing information before prescribing.}}

^{_{Further information is available from: UCB Pharma (Hong Kong) Limited}}

^{_{Ref.: HK PI 13-Sep-2021 (Tabs), July 2017 (OS), Nov 2017 (IV)]}}
 

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