Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies

Expanded access program results

CBD EAP study group

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objective: Since 2014, cannabidiol (CBD) has been administered to patients with treatment-resistant epilepsies (TREs) in an ongoing expanded-access program (EAP). We report interim results on the safety and efficacy of CBD in EAP patients treated through December 2016. Methods: Twenty-five US-based EAP sites enrolling patients with TRE taking stable doses of antiepileptic drugs (AEDs) at baseline were included. During the 4-week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received oral CBD starting at 2-10 mg/kg/d, titrated to a maximum dose of 25-50 mg/kg/d. Patient visits were every 2-4 weeks through 16 weeks and every 2-12 weeks thereafter. Efficacy endpoints included the percentage change from baseline in median monthly convulsive and total seizure frequency, and percentage of patients with ≥50%, ≥75%, and 100% reductions in seizures vs baseline. Data were analyzed descriptively for the efficacy analysis set and using the last-observation-carried-forward method to account for missing data. Adverse events (AEs) were documented at each visit. Results: Of 607 patients in the safety dataset, 146 (24%) withdrew; the most common reasons were lack of efficacy (89 [15%]) and AEs (32 [5%]). Mean age was 13 years (range, 0.4-62). Median number of concomitant AEDs was 3 (range, 0-10). Median CBD dose was 25 mg/kg/d; median treatment duration was 48 weeks. Add-on CBD reduced median monthly convulsive seizures by 51% and total seizures by 48% at 12 weeks; reductions were similar through 96 weeks. Proportion of patients with ≥50%, ≥75%, and 100% reductions in convulsive seizures were 52%, 31%, and 11%, respectively, at 12 weeks, with similar rates through 96 weeks. CBD was generally well tolerated; most common AEs were diarrhea (29%) and somnolence (22%). Significance: Results from this ongoing EAP support previous observational and clinical trial data showing that add-on CBD may be an efficacious long-term treatment option for TRE.

Original languageEnglish (US)
Pages (from-to)1540-1548
Number of pages9
JournalEpilepsia
Volume59
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Cannabidiol
Epilepsy
Seizures
Safety
Anticonvulsants
Therapeutics
Patient Safety
Caregivers
Diarrhea
Parents
Observation
Clinical Trials

Keywords

  • cannabidiol
  • efficacy
  • expanded access program
  • seizures
  • tolerability
  • treatment-resistant epilepsy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies : Expanded access program results. / CBD EAP study group.

In: Epilepsia, Vol. 59, No. 8, 01.08.2018, p. 1540-1548.

Research output: Contribution to journalArticle

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title = "Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results",
abstract = "Objective: Since 2014, cannabidiol (CBD) has been administered to patients with treatment-resistant epilepsies (TREs) in an ongoing expanded-access program (EAP). We report interim results on the safety and efficacy of CBD in EAP patients treated through December 2016. Methods: Twenty-five US-based EAP sites enrolling patients with TRE taking stable doses of antiepileptic drugs (AEDs) at baseline were included. During the 4-week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received oral CBD starting at 2-10 mg/kg/d, titrated to a maximum dose of 25-50 mg/kg/d. Patient visits were every 2-4 weeks through 16 weeks and every 2-12 weeks thereafter. Efficacy endpoints included the percentage change from baseline in median monthly convulsive and total seizure frequency, and percentage of patients with ≥50{\%}, ≥75{\%}, and 100{\%} reductions in seizures vs baseline. Data were analyzed descriptively for the efficacy analysis set and using the last-observation-carried-forward method to account for missing data. Adverse events (AEs) were documented at each visit. Results: Of 607 patients in the safety dataset, 146 (24{\%}) withdrew; the most common reasons were lack of efficacy (89 [15{\%}]) and AEs (32 [5{\%}]). Mean age was 13 years (range, 0.4-62). Median number of concomitant AEDs was 3 (range, 0-10). Median CBD dose was 25 mg/kg/d; median treatment duration was 48 weeks. Add-on CBD reduced median monthly convulsive seizures by 51{\%} and total seizures by 48{\%} at 12 weeks; reductions were similar through 96 weeks. Proportion of patients with ≥50{\%}, ≥75{\%}, and 100{\%} reductions in convulsive seizures were 52{\%}, 31{\%}, and 11{\%}, respectively, at 12 weeks, with similar rates through 96 weeks. CBD was generally well tolerated; most common AEs were diarrhea (29{\%}) and somnolence (22{\%}). Significance: Results from this ongoing EAP support previous observational and clinical trial data showing that add-on CBD may be an efficacious long-term treatment option for TRE.",
keywords = "cannabidiol, efficacy, expanded access program, seizures, tolerability, treatment-resistant epilepsy",
author = "{CBD EAP study group} and Szaflarski, {Jerzy P.} and Bebin, {Elizabeth Martina} and Comi, {Anne M.} and Patel, {Anup D.} and Charuta Joshi and Daniel Checketts and Beal, {Jules C.} and Laux, {Linda C.} and {De Boer}, {Lisa M.} and Wong, {Matthew H.} and Merrick Lopez and Orrin Devinsky and Lyons, {Paul D.} and Zentil, {Pilar Pichon} and Robert Wechsler and Michael Chez and Robert Flamini and Marsh, {Eric D.} and Ian Miller and Yong Park and Eric Segal and Laurie Seltzer and Thiele, {Elizabeth A.} and Park, {Yong D}",
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T1 - Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies

T2 - Expanded access program results

AU - CBD EAP study group

AU - Szaflarski, Jerzy P.

AU - Bebin, Elizabeth Martina

AU - Comi, Anne M.

AU - Patel, Anup D.

AU - Joshi, Charuta

AU - Checketts, Daniel

AU - Beal, Jules C.

AU - Laux, Linda C.

AU - De Boer, Lisa M.

AU - Wong, Matthew H.

AU - Lopez, Merrick

AU - Devinsky, Orrin

AU - Lyons, Paul D.

AU - Zentil, Pilar Pichon

AU - Wechsler, Robert

AU - Chez, Michael

AU - Flamini, Robert

AU - Marsh, Eric D.

AU - Miller, Ian

AU - Park, Yong

AU - Segal, Eric

AU - Seltzer, Laurie

AU - Thiele, Elizabeth A.

AU - Park, Yong D

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Objective: Since 2014, cannabidiol (CBD) has been administered to patients with treatment-resistant epilepsies (TREs) in an ongoing expanded-access program (EAP). We report interim results on the safety and efficacy of CBD in EAP patients treated through December 2016. Methods: Twenty-five US-based EAP sites enrolling patients with TRE taking stable doses of antiepileptic drugs (AEDs) at baseline were included. During the 4-week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received oral CBD starting at 2-10 mg/kg/d, titrated to a maximum dose of 25-50 mg/kg/d. Patient visits were every 2-4 weeks through 16 weeks and every 2-12 weeks thereafter. Efficacy endpoints included the percentage change from baseline in median monthly convulsive and total seizure frequency, and percentage of patients with ≥50%, ≥75%, and 100% reductions in seizures vs baseline. Data were analyzed descriptively for the efficacy analysis set and using the last-observation-carried-forward method to account for missing data. Adverse events (AEs) were documented at each visit. Results: Of 607 patients in the safety dataset, 146 (24%) withdrew; the most common reasons were lack of efficacy (89 [15%]) and AEs (32 [5%]). Mean age was 13 years (range, 0.4-62). Median number of concomitant AEDs was 3 (range, 0-10). Median CBD dose was 25 mg/kg/d; median treatment duration was 48 weeks. Add-on CBD reduced median monthly convulsive seizures by 51% and total seizures by 48% at 12 weeks; reductions were similar through 96 weeks. Proportion of patients with ≥50%, ≥75%, and 100% reductions in convulsive seizures were 52%, 31%, and 11%, respectively, at 12 weeks, with similar rates through 96 weeks. CBD was generally well tolerated; most common AEs were diarrhea (29%) and somnolence (22%). Significance: Results from this ongoing EAP support previous observational and clinical trial data showing that add-on CBD may be an efficacious long-term treatment option for TRE.

AB - Objective: Since 2014, cannabidiol (CBD) has been administered to patients with treatment-resistant epilepsies (TREs) in an ongoing expanded-access program (EAP). We report interim results on the safety and efficacy of CBD in EAP patients treated through December 2016. Methods: Twenty-five US-based EAP sites enrolling patients with TRE taking stable doses of antiepileptic drugs (AEDs) at baseline were included. During the 4-week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received oral CBD starting at 2-10 mg/kg/d, titrated to a maximum dose of 25-50 mg/kg/d. Patient visits were every 2-4 weeks through 16 weeks and every 2-12 weeks thereafter. Efficacy endpoints included the percentage change from baseline in median monthly convulsive and total seizure frequency, and percentage of patients with ≥50%, ≥75%, and 100% reductions in seizures vs baseline. Data were analyzed descriptively for the efficacy analysis set and using the last-observation-carried-forward method to account for missing data. Adverse events (AEs) were documented at each visit. Results: Of 607 patients in the safety dataset, 146 (24%) withdrew; the most common reasons were lack of efficacy (89 [15%]) and AEs (32 [5%]). Mean age was 13 years (range, 0.4-62). Median number of concomitant AEDs was 3 (range, 0-10). Median CBD dose was 25 mg/kg/d; median treatment duration was 48 weeks. Add-on CBD reduced median monthly convulsive seizures by 51% and total seizures by 48% at 12 weeks; reductions were similar through 96 weeks. Proportion of patients with ≥50%, ≥75%, and 100% reductions in convulsive seizures were 52%, 31%, and 11%, respectively, at 12 weeks, with similar rates through 96 weeks. CBD was generally well tolerated; most common AEs were diarrhea (29%) and somnolence (22%). Significance: Results from this ongoing EAP support previous observational and clinical trial data showing that add-on CBD may be an efficacious long-term treatment option for TRE.

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KW - efficacy

KW - expanded access program

KW - seizures

KW - tolerability

KW - treatment-resistant epilepsy

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