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

Orrin Devinsky, Chloe Verducci, Elizabeth A. Thiele, Linda C. Laux, Anup D. Patel, Francis Filloux, Jerzy P. Szaflarski, Angus Wilfong, Gary D. Clark, Yong D Park, Laurie E. Seltzer, E. Martina Bebin, Robert Flamini, Robert T. Wechsler, Daniel Friedman

Research output: Contribution to journalArticle

23 Citations (Scopus)

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, χ 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 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.

Original languageEnglish (US)
Pages (from-to)131-137
Number of pages7
JournalEpilepsy and Behavior
Volume86
DOIs
StatePublished - Sep 1 2018

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Cannabidiol
Epilepsy
Seizures
Safety
Aicardi Syndrome
Compassionate Use Trials
Lost to Follow-Up
Brain Diseases
Patient Safety
Therapeutics
Randomized Controlled Trials
Placebos
Research Personnel
Observation
Prospective Studies
Pharmaceutical Preparations
Population

Keywords

  • Aicardi syndrome
  • CDKL5 deficiency disorder
  • Cannabidiol
  • Doose syndrome
  • Dup15q syndrome

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Behavioral Neuroscience

Cite this

Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. / Devinsky, Orrin; Verducci, Chloe; Thiele, Elizabeth A.; Laux, Linda C.; Patel, Anup D.; Filloux, Francis; Szaflarski, Jerzy P.; Wilfong, Angus; Clark, Gary D.; Park, Yong D; Seltzer, Laurie E.; Bebin, E. Martina; Flamini, Robert; Wechsler, Robert T.; Friedman, Daniel.

In: Epilepsy and Behavior, Vol. 86, 01.09.2018, p. 131-137.

Research output: Contribution to journalArticle

Devinsky, O, Verducci, C, Thiele, EA, Laux, LC, Patel, AD, Filloux, F, Szaflarski, JP, Wilfong, A, Clark, GD, Park, YD, Seltzer, LE, Bebin, EM, Flamini, R, Wechsler, RT & Friedman, D 2018, 'Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes', Epilepsy and Behavior, vol. 86, pp. 131-137. https://doi.org/10.1016/j.yebeh.2018.05.013
Devinsky, Orrin ; Verducci, Chloe ; Thiele, Elizabeth A. ; Laux, Linda C. ; Patel, Anup D. ; Filloux, Francis ; Szaflarski, Jerzy P. ; Wilfong, Angus ; Clark, Gary D. ; Park, Yong D ; Seltzer, Laurie E. ; Bebin, E. Martina ; Flamini, Robert ; Wechsler, Robert T. ; Friedman, Daniel. / Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. In: Epilepsy and Behavior. 2018 ; Vol. 86. pp. 131-137.
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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, χ 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 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.",
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AU - Thiele, Elizabeth A.

AU - Laux, Linda C.

AU - Patel, Anup D.

AU - Filloux, Francis

AU - Szaflarski, Jerzy P.

AU - Wilfong, Angus

AU - Clark, Gary D.

AU - Park, Yong D

AU - Seltzer, Laurie E.

AU - Bebin, E. Martina

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N2 - 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, χ 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 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.

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