Open-label use of highly purified CBD (Epidiolex(R)) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes

Devinsky, O.; Verducci, C.; Thiele, E. A.; Laux, L. C.; Patel, A. D.; Filloux, F.; Szaflarski, J. P.; Wilfong, A.; Clark, G. D.; Park, Y. D.; Seltzer, L. E.; Bebin, E. M.; Flamini, R.; Wechsler, R. T.; Friedman, D.

Epilepsy Behav. 2018 Jul 15; 86:131-137

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 1-30years with severe childhood-onset epilepsy who received CBD for >/=10weeks 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, chi(2)(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 12weeks to 48weeks 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.

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