Prof. Petr Marusič: Is the Success of Therapy Changing with the Arrival of New Antiepileptics?
At the XXV. postgraduate course in epileptology, 'Jiří Dolanský Days', prof. MUDr. Petr Marusič, Ph.D., from the Neurological Clinic of the 2nd Faculty of Medicine, Charles University, and Motol University Hospital, lectured on the topic of changes in the efficacy of epilepsy treatment with the arrival of new anti-seizure medications.
Introduction
The main goal of epilepsy treatment is the disappearance of seizures. The author of the message reminded us at the beginning that patients with persistent seizures are at a higher risk of premature death (injuries, SUDEP − sudden unexpected death in epilepsy), suffer from psychiatric comorbidities (depression, anxiety), and adverse effects of concurrently used antiepileptics. All these consequences contribute to a reduced quality of life. Disappearance of seizures, on the other hand, leads to cognitive improvement of patients.
New ASM Modalities and Their Impact on Patient Compensation
According to data from 2000, compensation with the first anti-seizure medication (ASM − anti-seizure medication) was achieved on average in 50% of patients [1]. After the introduction of a second ASM, another 15% of patients were compensated, and with a third ASM, about an additional 5%. Therefore, 30% of patients who did not respond to the treatment and continued to suffer from seizures remained.
After 2000, however, new ASMs gradually began to enter the market, and it was possible to test their effect on non-compensated patients. Professor Marusič mentioned, for example, the results of a study from 2007, which included 155 non-compensated patients [2]. With the introduction of the first ASM, 17% of them were compensated, with the second ASM another 14%, and with the third ASM 15% more. Additionally, 28% of participants completely stopped having seizures.
Another example of the success of new ASMs was a newer study from 2017 with 144 refractory patients [3]. By systematically testing and introducing new ASMs (lacosamide, n = 65; perampanel, n = 30; eslicarbazepine, n = 29; retigabine, n = 14), it was possible to achieve the disappearance of seizures in almost 14% of participants after 6 months.
Professor Marusič therefore recommends trying new ASM modalities in refractory patients, for whom another introduced medication may offer a chance for seizure control. ASMs are a heterogeneous group of substances that affect various pathophysiological processes − it is therefore suitable to test further options in most previously refractory patients, even if they may benefit only one in ten. However, it should be added that data from sufficiently long-term monitoring of the effect of new ASMs are not yet available. Another aspect that obviously needs to be monitored is then the adverse side effects of new ASMs (for example, behavioral) and the overall tolerability of the treatment.
Measuring ASM Levels
Examining plasma ASM levels can help in assessing drug interactions, suspicion of toxicity, monitoring patient adherence, and identifying other causes of insufficient compensation. Determining ASM levels is appropriate after reaching the steady-state and should be taken at the same time of day for a given patient (depending on the time of dose intake). Otherwise, individual values cannot be compared with each other.
According to Professor Marusič, he does not recommend adjusting the dosage based on the determined values because the reference range is individual. An increased plasma ASM level is not a reason to reduce the dose in a compensated patient who tolerates the dose well. On the contrary, for a patient who, although in the reference range, is not compensated, it is advisable to try to increase the dose.
Conclusion
'According to last year's EpiStop guidelines, we have 14 drugs for focal seizures available, both for monotherapy of the 1st or 2nd choice, as well as in the context of adjuvant therapy. We have much to try with patients, and we should systematically do so in refractory cases. If treatment has failed on previous modalities, it does not mean that patients cannot be seizure-free on something new,' the author summarized his perspective on current approaches to treatment in conclusion. You can watch his entire lecture recorded here.
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Sources:
1. Kwan P., Brodie M. J. Early identification of refractory epilepsy. N Engl J Med 2000; 342 (5): 314–319, doi: 10.1056/NEJM200002033420503.
2. Luciano A. L., Shorvon S. D. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol 2007; 62 (4): 375–381, doi: 10.1002/ana.21064.
3. Martínez-Lizana E., Gil-Lopez F., Donaire A. et al. Outcome of treatment changes in patients with drug-resistant chronic epilepsy: a tertiary center experience. Epilepsy Res 2017; 136: 97–102, doi: 10.1016/j.eplepsyres.2017.07.011.
4. Minimal diagnostic and therapeutic standards for patients with epilepsy. EpiStop, 2021. Available at: www.epistop.cz/images/publications/Epistandards_2021_08_web.pdf
5. Marusič P. Is the success of epilepsy treatment changing with the arrival of new medications? XXV. postgraduate course in epileptology, 'Jiří Dolanský Days', Prague, 7. 10. 2022. Available at: https://www.kongres.tv/epilepsie2v/on-the-way-to-a-life-without-seizures
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