Sunpharma

Date: {{$ActivityAssignDate}}

Dear Dr. {{ $doctorName }},

Subject : A survey to assess the usage pattern of Brivaracetam in the management of partial onset seizure in India

Epilepsy is characterized by recurrent seizures caused by abnormal neuronal discharges in the brain. ^{1. 2. 3.} Epilepsy is the third leading contributor to the global burden of disease for neurological disorders the global burden of disease for neurological disorders and affects 65 million people worldwide. ^{4. 5} According meta-analysis of international studies, the prevalence of epilepsy is 6.4 cases per 1,000 persons and the annual incidence is 67.8 cases per 100,000 person-years. 'It is estimated that there are more than 10 million persons with epilepsy (PWE) in India.⁷ Its prevalence is about 1% in our population. The prevalence is higher in the rural (1.9%) compared to urban population (0.6%).^8.9

Seizures can be broadly categorized into the following two types. ^{1, 2, 3} Partial onset seizures & generalized onset seizures. Partial onset seizures originate in, or are restricted to, a localized area of the brain, with the location of the abnormal neuronal discharge determining the phenomena associate with the seizure. Further classified as simple partial, complex partial or partial with secondary generalization¹⁰ ASDs (Anti-seizure drug) are the primary therapy for epilepsy and are symptomatic treatments that control seizures.¹¹ The choice of ASDs varies with different seizure types and epileptic syndromes. ¹²

Brivaracetam has high lipid solubility and rapid brain penetration, with engagement of target molecule, SV2A, within minutes of administration. BRV is selective, high-affinity ligand for synaptic vesicle 2A (SV2A) with 15-30-fold higher affinity than levetiracetam. Brivaracetam exhibits high permeability across the blood-brain barrier, likely because of its higher lipophilicity compared with levetiracetam, and binds with high selectivity to the synaptic vesicle protein 2A (SV2A) with 15- to 30-fold higher affinity than levetiracetam. ^{13. 14}

According to a Retrospective, Multicenter, Real World Study, Brivaracetam was effective and well tolerated both as first add-on and late adjunctive treatment in patients with focal epilepsy. ¹⁵

This survey has been undertaken to assess the usage pattern of brivaracetam in the management of partial onset seizures in India.

As you will be spending some extra time to give your feedback on the questionnaire based on your clinical experience, we offer to pay you by cheque a professional fee of Rs {{$contractAmount}}, on receiving the completed Survey Questionnaire Form from you.

We trust you and we are partners in promoting effective drug therapy. In that spirit we hope you will consent to participate in this survey. If you do, please sign and return the enclosed reply along with your visiting card for accuracy of records.

Yours truly,

Mr. Ravishankar Viswanathan

SVP & Cluster Head,

Sun Pharma laboratories Ltd

1 : National Institute for Clinical Excellence. Technology appraisal 76: newer drugs for epilepsy in adults. London: National Institute of Clinical Excellence, 2004 Mar

2 : National Institute for Clinical Excellence. Technology appraisal 79: newer drugs for epilepsy in children. London: National Institute of Clinical Excellence, 2004 Apr

3 : Proposal for revised classification of epilepsies and epileptic syndromes: commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1989; 30 (4): 389-99

4 : Prevalence Collaborators et al. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1545-1602 (2016)

5 : Ngugi, A. K.. Bottomley, C., Kleinschmidt, I., Sander, J. W. & Newton, C. R. Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia 51, 883-890 (2010).

6 : Fiest, K. M. et al. Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies. Neurology 88, 296-303 (2017).

7 : Leonardi M, Ustun TB. The global burden of epilepsy. Epilepsia 2002; 43(Suppl 6):21-5.

8 : Pahl K, de Boer HM. Epilepsy and rights. Atlas: Epilepsy Care in the World. Geneva: WHO; 2005. p. 72-3.

9 : Lyseng-Williamson KA. Levetiracetam: a review of its use in epilepsy. Drugs. 2011 Mar 5;71 (4):489-514.

10 : Pitkanen A. Therapeutic approaches to epileptogenesis-hope on the horizon. Epilepsia. 2010;51(Suppl 3):2-17

11 : Löscher W, Potschka H. et al. Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options. Pharmacol Rev. 2020 Jul;72(3):606-638/p>

12 : Mattson, R., Cramer, J., Collins, J. et al. Comparison of Carbamazepine, Phenobarbital phenytoin, and primidone is partial and secondarily generalized tonic-clonic seizures. New England Journal of Medicine

13 : Klein P, Diaz A, Gasalla T, Whitesides J. A review of the pharmacology and clinical efficacy of brivaracetam. Clin Pharmacol. 2018 Jan 19;10:1-22.

14 : Moseley BD, Chanteux H, Nicolas JM, et al. A review of the drug-drug interactions of the antiepileptic drug brivaracetam. Epilepsy Res. 2020 Jul;163:106327.

15 : Lattanzi S, Canafoglia L, Canevini MP, Casciato S, Cerulli Irelli E, Chiesa V, Dainese F, De Maria G, Didato G, Di Gennaro G, Falcicchio G, Fanella M, Ferlazzo E, Gangitano M, La Neve A, Mecarelli O, Montalenti E. Morano A, Piazza F, Pizzanelli C, Pulitano P, Ranzato F, Rosati E, Tassi L., Di Bonaventura C; BRIV Aracetam add-on First Italian network Study (BRIVAFIRST) Group. Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, Real-World Study. Neurol Ther 2022 Dec;11(4):1789-1804.