TY - JOUR
T1 - Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies
AU - Balestrini, Simona
AU - Chiarello, Daniela
AU - Gogou, Maria
AU - Silvennoinen, Katri
AU - Puvirajasinghe, Clinda
AU - Jones, Wendy D
AU - Reif, Philipp
AU - Klein, Karl Martin
AU - Rosenow, Felix
AU - Weber, Yvonne G
AU - Lerche, Holger
AU - Schubert-Bast, Susanne
AU - Borggraefe, Ingo
AU - Coppola, Antonietta
AU - Troisi, Serena
AU - Møller, Rikke S
AU - Riva, Antonella
AU - Striano, Pasquale
AU - Zara, Federico
AU - Hemingway, Cheryl
AU - Marini, Carla
AU - Rosati, Anna
AU - Mei, Davide
AU - Montomoli, Martino
AU - Guerrini, Renzo
AU - Cross, J Helen
AU - Sisodiya, Sanjay M
N1 - © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.
PY - 2021/10
Y1 - 2021/10
N2 - OBJECTIVE: The term 'precision medicine' describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy.METHODS: A systematic survey of patients with epilepsy with a molecular genetic diagnosis was conducted in six tertiary epilepsy centres including children and adults. A standardised questionnaire was used for data collection, including genetic findings and impact on clinical and therapeutic management.RESULTS: We included 293 patients with genetic epilepsies, 137 children and 156 adults, 162 females and 131 males. Treatment changes were undertaken because of the genetic findings in 94 patients (32%), including rational precision medicine treatment and/or a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms. There was a rational precision medicine treatment for 56 patients (19%), and this was tried in 33/56 (59%) and was successful (ie, >50% seizure reduction) in 10/33 (30%) patients. In 73/293 (25%) patients there was a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms, and this was successful in 24/73 (33%).SIGNIFICANCE: Our survey of clinical practice in specialised epilepsy centres shows high variability of clinical outcomes following the identification of a genetic cause for an epilepsy. Meaningful change in the treatment paradigm after genetic testing is not yet possible for many people with epilepsy. This systematic survey provides an overview of the current application of precision medicine in the epilepsies, and suggests the adoption of a more considered approach.
AB - OBJECTIVE: The term 'precision medicine' describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy.METHODS: A systematic survey of patients with epilepsy with a molecular genetic diagnosis was conducted in six tertiary epilepsy centres including children and adults. A standardised questionnaire was used for data collection, including genetic findings and impact on clinical and therapeutic management.RESULTS: We included 293 patients with genetic epilepsies, 137 children and 156 adults, 162 females and 131 males. Treatment changes were undertaken because of the genetic findings in 94 patients (32%), including rational precision medicine treatment and/or a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms. There was a rational precision medicine treatment for 56 patients (19%), and this was tried in 33/56 (59%) and was successful (ie, >50% seizure reduction) in 10/33 (30%) patients. In 73/293 (25%) patients there was a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms, and this was successful in 24/73 (33%).SIGNIFICANCE: Our survey of clinical practice in specialised epilepsy centres shows high variability of clinical outcomes following the identification of a genetic cause for an epilepsy. Meaningful change in the treatment paradigm after genetic testing is not yet possible for many people with epilepsy. This systematic survey provides an overview of the current application of precision medicine in the epilepsies, and suggests the adoption of a more considered approach.
U2 - 10.1136/jnnp-2020-325932
DO - 10.1136/jnnp-2020-325932
M3 - Article
C2 - 33903184
SN - 0022-3050
VL - 92
SP - 1044
EP - 1052
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
IS - 10
ER -