Orrin Devinsky1, Chloe Verducci2, Elizabeth A Thiele3, Linda C Laux4, Anup D Patel5, Francis Filloux6, Jerzy P Szaflarski7, Angus Wilfong8, Gary D Clark9, Yong D Park10, Laurie E Seltzer11, E Martina Bebin12, Robert Flamini13, Robert T Wechsler14, Daniel Friedman15. 1. New York University School of Medicine, NY, United States. Electronic address: od4@nyu.edu. 2. New York University School of Medicine, NY, United States. Electronic address: Chloe.verducci@nyumc.org. 3. Massachusetts General Hospital, MA, United States. Electronic address: ETHIELE@mgh.harvard.edu. 4. Lurie Children's Hospital of Chicago, IL, United States. Electronic address: LLaux@luriechildrens.org. 5. Nationwide Children's Hospital, OH, United States. Electronic address: Anup.Patel@nationwidechildrens.org. 6. Utah School of Medicine, UT, United States. Electronic address: Francis.Filloux@hsc.utah.edu. 7. UAB Epilepsy Center, 1719 6th Avenue South, CIRC 312, Birmingham, AL 35294, United States. Electronic address: jszaflarski@uabmc.edu. 8. Texas Children's Hospital, Houston, TX, United States; Baylor College of Medicine, Houston, TX, United States. Electronic address: awilfong@phoenixchildrens.com. 9. Neurology and Neuroscience, Baylor College of Medicine, TX, United States; Neurology Service, Texas Children's Hospital, United States; Professors of Child Neurology, United States. Electronic address: gdclark@texaschildrens.org. 10. Neurology and Pediatrics, Medical College of Georgia, Augusta University, GA, United States; Child Neurology, Medical College of Georgia, Augusta University, United States. Electronic address: YPARK@augusta.edu. 11. University of Rochester Medical Center, NY, United States. Electronic address: Laurie_Seltzer@URMC.Rochester.edu. 12. Neurology and Pediatrics, UAB Epilepsy Center, Birmingham, AL 35294, United States. Electronic address: ebebin@uabmc.edu. 13. PANDA Neurology (Pediatric and Adolescent NeuroDevelopmental Associates), Atlanta, GA, United States. 14. Consultants in Epilepsy & Neurology, 1499 West Hays Street, Boise, ID 83702, United States; Idaho Comprehensive Epilepsy Center, 1499 West Hays Street, Boise, ID 83702, United States. 15. New York University School of Medicine, NY, United States. Electronic address: Daniel.friedman@nyumc.org.
Abstract
OBJECTIVE: We studied our collective open-label, compassionate use experience in using cannabidiol (CBD) to treat epilepsy in patients with CDKL5 deficiency disorder and Aicardi, Doose, and Dup15q syndromes. METHODS: We included patients aged 1-30 years with severe childhood-onset epilepsy who received CBD for ≥10 weeks as part of multiple investigator-initiated expanded access or state access programs for a compassionate prospective interventional study: CDKL5 deficiency disorder (n = 20), Aicardi syndrome (n = 19), Dup15q syndrome (n = 8), and Doose syndrome (n = 8). These patients were treated at 11 institutions from January 2014 to December 2016. RESULTS: The percent change in median convulsive seizure frequency for all patients taking CBD in the efficacy group decreased from baseline [n = 46] to week 12 (51.4% [n = 35], interquartile range (IQR): 9-85%) and week 48 (59.1% [n = 27], IQR: 14-86%). There was a significant difference between the percent changes in monthly convulsive seizure frequency during baseline and week 12, χ2(2) = 22.9, p = 0.00001, with no difference in seizure percent change between weeks 12 and 48. Of the 55 patients in the safety group, 15 (27%) withdrew from extended observation by week 144: 4 due to adverse effects, 9 due to lack of efficacy, 1 withdrew consent, and 1 was lost to follow-up. SIGNIFICANCE: This open-label drug trial provides class III evidence for the long-term safety and efficacy of CBD administration in patients with treatment-resistant epilepsy (TRE) associated with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Adjuvant therapy with CBD showed similar safety and efficacy for these four syndromes as reported in a diverse population of TRE etiologies. This study extended analysis of the prior report from 12 weeks to 48 weeks of efficacy data and suggested that placebo-controlled randomized trials should be conducted to formally assess the safety and efficacy of CBD in these epileptic encephalopathies.
OBJECTIVE: We studied our collective open-label, compassionate use experience in using cannabidiol (CBD) to treat epilepsy in patients with CDKL5 deficiency disorder and Aicardi, Doose, and Dup15q syndromes. METHODS: We included patients aged 1-30 years with severe childhood-onset epilepsy who received CBD for ≥10 weeks as part of multiple investigator-initiated expanded access or state access programs for a compassionate prospective interventional study: CDKL5 deficiency disorder (n = 20), Aicardi syndrome (n = 19), Dup15q syndrome (n = 8), and Doose syndrome (n = 8). These patients were treated at 11 institutions from January 2014 to December 2016. RESULTS: The percent change in median convulsive seizure frequency for all patients taking CBD in the efficacy group decreased from baseline [n = 46] to week 12 (51.4% [n = 35], interquartile range (IQR): 9-85%) and week 48 (59.1% [n = 27], IQR: 14-86%). There was a significant difference between the percent changes in monthly convulsive seizure frequency during baseline and week 12, χ2(2) = 22.9, p = 0.00001, with no difference in seizure percent change between weeks 12 and 48. Of the 55 patients in the safety group, 15 (27%) withdrew from extended observation by week 144: 4 due to adverse effects, 9 due to lack of efficacy, 1 withdrew consent, and 1 was lost to follow-up. SIGNIFICANCE: This open-label drug trial provides class III evidence for the long-term safety and efficacy of CBD administration in patients with treatment-resistant epilepsy (TRE) associated with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Adjuvant therapy with CBD showed similar safety and efficacy for these four syndromes as reported in a diverse population of TRE etiologies. This study extended analysis of the prior report from 12 weeks to 48 weeks of efficacy data and suggested that placebo-controlled randomized trials should be conducted to formally assess the safety and efficacy of CBD in these epilepticencephalopathies.
Authors: Heather E Olson; Scott T Demarest; Elia M Pestana-Knight; Lindsay C Swanson; Sumaiya Iqbal; Dennis Lal; Helen Leonard; J Helen Cross; Orrin Devinsky; Tim A Benke Journal: Pediatr Neurol Date: 2019-02-23 Impact factor: 3.372
Authors: Scott Demarest; Elia M Pestana-Knight; Heather E Olson; Jenny Downs; Eric D Marsh; Walter E Kaufmann; Carol-Anne Partridge; Helen Leonard; Femida Gwadry-Sridhar; Katheryn Elibri Frame; J Helen Cross; Richard F M Chin; Sumit Parikh; Axel Panzer; Judith Weisenberg; Karen Utley; Amanda Jaksha; Sam Amin; Omar Khwaja; Orrin Devinsky; Jeffery L Neul; Alan K Percy; Tim A Benke Journal: Pediatr Neurol Date: 2019-03-27 Impact factor: 3.372
Authors: Rishabh Verma; Farazul Hoda; Mawrah Arshad; Asif Iqubal; Ali Nasir Siddiqui; Mohammad Ahmed Khan; Syed Ehtaishamul Haque; Mohd Akhtar; Abul Kalam Najmi Journal: Med Cannabis Cannabinoids Date: 2021-05-21
Authors: Bin Gu; Manhua Zhu; Madison R Glass; Marie Rougié; Viktoriya D Nikolova; Sheryl S Moy; Paul R Carney; Benjamin D Philpot Journal: J Clin Invest Date: 2019-12-02 Impact factor: 14.808
Authors: Marieka V DeVuono; Olivia La Caprara; Gavin N Petrie; Cheryl L Limebeer; Erin M Rock; Matthew N Hill; Linda A Parker Journal: Cannabis Cannabinoid Res Date: 2020-12-21
Authors: Lu Hou; Jian Rong; Ahmed Haider; Daisuke Ogasawara; Cassis Varlow; Michael A Schafroth; Linjing Mu; Jiefeng Gan; Hao Xu; Christopher J Fowler; Ming-Rong Zhang; Neil Vasdev; Simon Ametamey; Benjamin F Cravatt; Lu Wang; Steven H Liang Journal: J Med Chem Date: 2020-12-30 Impact factor: 7.446
Authors: Colleen Pawliuk; Briana Chau; S Rod Rassekh; Terri McKellar; Harold Hal Siden Journal: Paediatr Child Health Date: 2020-04-30 Impact factor: 2.253