Preview

Epilepsy and paroxysmal conditions

Advanced search

Efficacy assessment of levetiracetam monotherapy in newly-diagnosed epilepsy in adults using epileptiform activity index

https://doi.org/10.17749/2077-8333/epi.par.con.2020.024

Abstract

Abstract. Levetiracetam (LEV) is one of the most commonly prescribed antiepileptic drugs (AED). However, there were no studies on its efficacy and safety in terms of the correlation with epileptiform activity index (EAI) performed among the Russian population.

Aim. To evaluate the efficacy and tolerability of LEV monotherapy in patients with newly-diagnosed epilepsy using epileptiform activity index (EAI) assessment.

Materials and methods. The study included 107 patients (46 (43.0%) male and 61 (57.0%) female) with focal epilepsy (FE) (39.3%; n=42) or idiopathic generalized epilepsy (IGE) (60.7%; n=65). At each visit, video-electroencephalographic (video-EEG) monitoring was performed (baseline and in 1, 3, 6, and 12 months of the therapy). Therapeutic drug monitoring was performed at dose titration in 1 month of the therapy or in case of therapy correction. Treatment efficacy was assessed using the criteria of seizure absence (medically induced remission), seizure rate decrease by >50% (responders), seizure rate decrease by <50% – insufficient efficacy, a composite index of efficacy/tolerability (retention on treatment), and seizure rate increase compared to baseline and/or development of a new type of seizures (aggravation). Adverse events (AE) were assessed using the scale for side effects in AED treatment (SIDAED).

Results. Total EAI at baseline was 5.2-fold higher in patients with IGE compared to FE patients (23.4±3.0 and 4.5±0.97, respectively). After 1 month of LEV therapy, EAI decreased to 3.4±1.1 and 1.9±0.4 in patients with IGE and FE, respectively (p<0.01). The decrease continued during the whole follow-up period. Retention on monotherapy was achieved in 82.2% (n=88/107) patients; in 87.6% (n=57/65) patients with IGE and in 73.8% (n=31/42) with FE. The rate of serious AEs during the follow-up period was 8.4% (n=9).

Conclusions. LEV is an effective drug of choice for the initial treatment of newly-diagnosed FE and IGE in monotherapy along with a significant decrease in EAI. EAI is an objective measure of LEV treatment efficacy.

About the Authors

V. A. Karlov
A. I. Evdokimov Moscow State University of Medicine and Dentistry
Russian Federation

Vladimir A. Karlov – Honored Scientist of the Russian Federation, Associate Member of the Russian Academy of Sciences, MD, Dr Sci Med; Professor of Chair of Neurology, Department of General Medicine; President of the Russian League Against Epilepsy (RLAE) – ILAE Russian Chapter, Scopus ID: 7103065003, SPIN RSCI: 2726-9790, 20-1 Delegatskaya Str., Moscow 127473, Russia



A. B. Kozhokaru
State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency
Russian Federation

Angela B. Kozhokaru – MD, PhD, Head of the laboratory of clinical neurophysiology, Associate Professor, Department of Neurology, Central state medical Academy of the Presidential administration of the Russian Federation, SPIN RSCI: 1019434, Scopus Author ID: 28367717700, 46 Zhivopisnaya Str., Moscow 123182, Russia



P. N. Vlasov
A. I. Evdokimov Moscow State University of Medicine and Dentistry
Russian Federation

Pavel N. Vlasov – MD, Dr Sci Med, Professor, Department of Nervous Diseases, Faculty of Medicine, SPIN RSCI: 701071, Scopus Author ID: 7101688064, 20-1 Delegatskaya Str., Moscow 127473, Russia



A. S. Samoilov
State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency
Russian Federation

Alexander S. Samoilov – MD, Dr Sci Med, Professor, Corresponding Member of the Russian Academy of Sciences, General Director, SPIN RSCI: 738843, Scopus Author ID: 57200643078, 46 Zhivopisnaya Str., Moscow 123182, Russia



Yu. D. Udalov
State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency
Russian Federation

Yuri D. Udalov – MD, Dr Sci Med, Associate Professor, Deputy General Director for Medical Affairs, Scopus Author ID: 57194193916, SPIN RSCI: 912296, 46 Zhivopisnaya Str., Moscow 123182, Russia



References

1. Karlov V. A. Epilepsy in children and adults, women and men. A guide for doctors. Second edition. Moscow: Publishing House BINOM. 2019; 896 p. (in Russ).

2. Beghi E. Addressing the burden of epilepsy: many unmet needs. Pharmacol Res. 2016; 107: 79–84.

3. Giussani G., Enia G., Bianchi E., et al.; EPINEEDS Study Group. The management of epilepsy in clinical practice: Do the needs manifested by the patients correspond to the priorities of the caring physicians? Findings from the EPINEEDS Study. Epilepsy Behav. 2020; 102: 106641. https://doi.org/10.1016/j.yebeh.2019.106641.

4. Glauser T., Ben-Menachem E., Bourgeois B., et al.; ILAE Subcommission on AED Guidelines. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2013; 54 (3): 551–63. https://doi.org/10.1111/epi.12074.

5. Ito S., Yano I., Hashi S., et al. Population Pharmacokinetic Modeling of Levetiracetam in Pediatric and Adult Patients With Epilepsy by Using Routinely Monitored Data. Therapeutic drug monitoring. 2016; 38: 371–378. https://doi.org/10.1097/FTD.0000000000000291.

6. Karlov V. A., Vlasov P. N., Zhidkova I. A. An open-label prospective clinical study of the efficacy and tolerability of brand-name and generic levetiracetam in the monotherapy of focal epilepsy in adults. Neurology, Neuropsychiatry, Psychosomatics. 2018;10(1S):12-17. (In Russ.) https://doi.org/10.14412/2074-2711-2018-1S-12-17.

7. Nevitt S. J., Sudell M., Weston J. et al. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. Cochrane Database Syst Rev. 2017; 6: CD011412. https://doi.org/10.1002/14651858.CD011412.pub2.

8. Mazur R. D., Wang Ba Q., Kato Bs K., et al. Effectiveness of Levetiracetam Monotherapy in Pediatric Patients With Epilepsy. J Child Neurol. 2019; 34 (10): 593–597. https://doi.org/10.1177/0883073819846804.

9. Arican P., Gencpinar P., Cavusoglu D., Olgac Dundar N. Levetiracetam monotherapy for the treatment of infants with epilepsy. Seizure. 2018; 56: 73–77. https://doi.org/10.1016/j.seizure.2018.02.006.

10. Wright C., Downing J., Mungall D., et al. Clinical pharmacology and pharmacokinetics of levetiracetam. Frontiers in neurology. 2013; 4, 192. https://doi.org/10.3389/fneur.2013.00192.

11. Nei S. D., Wittwer E. D., Kashani K. B., Frazee E. N. Levetiracetam Pharmacokinetics in a Patient Receiving Continuous Venovenous Hemofiltration and Venoarterial Extracorporeal Membrane Oxygenation. Pharmacotherapy. 2013; 35: 127–30. https://doi.org/10.1002/phar.1615.

12. Noyer M., Gillard M., Matagne A., et al. The novel antiepileptic drug levetiracetam (ucb L059) appears to act via a specific binding site in CNS membranes. Eur. J. Pharmacol. 1995; 286 (2): 137-46. https://doi.org/10.1016/0014-2999(95)00436-o.

13. Johannessen Landmark C., Patsalos P. N. Drug interactions involving the new second and third generation antiepileptic drugs. Expert Rev Neurother. 2010; 10: 119–40. https://doi.org/10.1586/ern.09.136.

14. Patsalos P. N., Spencer E. P., Berry D. J. Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update. Ther Drug Monit. 2018; 40 (5): 526–548. https://doi.org/10.1097/FTD.0000000000000546.

15. Rudakova I. G., Kotov A. S., Kotov S. V., Belova Yu.A., Lavrent’eva N. S. Levetiracetam (Keppra) in the treatment of various epileptic syndromes in adults. Zhurnal nevrologii i psikhiatrii im. C. C. Korsakova. 2009; 109 (10): 25–29. (in Russ).

16. Mukhin K. Yu., Tysyachina M. D., Petrukhin A. S. Levetiracetam in the treatment of juvenile myoclonic epilepsy (preliminary results). Russkii zhurnal detskoi nevrologii. 2009; 4 (1): 3–11. (in Russ).

17. Prokhorova A. V., Abidov I. A., Babadzhanova N. P. Effectiveness of levetiracetam in the treatment of symptomatic temporal lobe epilepsy in adults. Zhurnal teoreticheskoi i klinicheskoi meditsiny. 2014; 5: 129–132. (in Russ).

18. Toropina G. G. Levetiracetam in the treatment of epilepsy own experience of use in adult patients. Meditsinskii sovet. 2017; 10: 60–64. (in Russ).

19. Vlasov P. N., Karlov V. A., Kamel’kova E. G. Results of monotherapy with levetiracetam for partial epilepsy in adults. Zhurnal nevropatologii i psikhiatrii. 2010; (11): 15–20. (in Russ).

20. Vlasov P. N., Karlov V. A., Komelkova E. G., Shakhabasova Z. S. Long-term levetiracetam monotherapy for partial epilepsy in adults. Neurology, Neuropsychiatry, Psychosomatics. 2012; 4 (1S): 43–47. (In Russ.) https://doi.org/10.14412/2074-2711-2012-2498.

21. Borovkova N. A., Malov A. G. Efficacy of levetiracetam monotherapy in epilepsy associated with benign epileptiform discharges of childhood. Epilepsy and paroxysmal conditions. 2019; 11 (1): 63–68. (In Russ.) https://doi.org/10.17749/2077-8333.2019.11.1.63-68.

22. Fisher R. S., Acevedo C., Arzimanoglou A., et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014; 55 (4): 475–82. https://doi.org/10.1111/epi.12550.

23. Scheffer I. E., Berkovic S., Capovilla G., et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017; 58 (4): 512–521. https://doi.org/10.1111/epi.13709.

24. Alrabiah H. Levetiracetam. Profiles Drug Subst Excip Relat Methodol. 2019; 44: 167–204. https://doi.org/10.1016/bs.podrm.2019.02.003.

25. Yan H. D., Ji-qun C., Ishihara K. et al. Separation of antiepileptogenic and antiseizure effects of levetiracetam in the spontaneously epileptic rat (SER). Epilepsia. 2005; 46 (8): 1170–7. https://doi.org/10.1111/j.1528-1167.2005.2035204.x.

26. Sourbron J., Chan H., Wammes-van der Heijden E. A., et al. Review on the relevance of therapeutic drug monitoring of levetiracetam Jo Sourbrona. Seizure. 2018; 62: 131–135. https://doi.org/10.1016/j.seizure.2018.09.004.

27. Coppola G., Mangano S., Tortorella G., et al. Levetiracetam during 1-year follow-up in children, adolescents, and young adults with refractory epilepsy. Epilepsy Res. 2004; 59 (1): 35–42.

28. Nakken K. O., Eriksson A. S., Lossius R., Johannessen S. I. A paradoxical effect of levetiracetam may be seen in both children and adults with refractory epilepsy. Seizure. 2003; 12 (1): 42–6.


Review

For citations:


Karlov V.A., Kozhokaru A.B., Vlasov P.N., Samoilov A.S., Udalov Yu.D. Efficacy assessment of levetiracetam monotherapy in newly-diagnosed epilepsy in adults using epileptiform activity index. Epilepsy and paroxysmal conditions. 2020;12(2):93-104. (In Russ.) https://doi.org/10.17749/2077-8333/epi.par.con.2020.024

Views: 1338


ISSN 2077-8333 (Print)
ISSN 2311-4088 (Online)