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

Expanded access program results

Jerzy P. Szaflarski, Elizabeth Martina Bebin, Anne M. Comi, Anup D. Patel, Charuta Joshi, Daniel Checketts, Jules C. Beal, Linda C. Laux, Lisa M. De Boer, Matthew H. Wong, Merrick Lopez, Orrin Devinsky, Paul D. Lyons, Pilar Pichon Zentil, Robert Wechsler

Research output: Contribution to journalArticle

29 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)
JournalEpilepsia
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

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

Szaflarski, J. P., Bebin, E. M., Comi, A. M., Patel, A. D., Joshi, C., Checketts, D., ... Wechsler, R. (Accepted/In press). Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results. Epilepsia. https://doi.org/10.1111/epi.14477

Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies : Expanded access program results. / Szaflarski, Jerzy P.; Bebin, Elizabeth Martina; Comi, Anne M.; Patel, Anup D.; Joshi, Charuta; Checketts, Daniel; Beal, Jules C.; Laux, Linda C.; De Boer, Lisa M.; Wong, Matthew H.; Lopez, Merrick; Devinsky, Orrin; Lyons, Paul D.; Zentil, Pilar Pichon; Wechsler, Robert.

In: Epilepsia, 01.01.2018.

Research output: Contribution to journalArticle

Szaflarski, JP, Bebin, EM, Comi, AM, Patel, AD, Joshi, C, Checketts, D, Beal, JC, Laux, LC, De Boer, LM, Wong, MH, Lopez, M, Devinsky, O, Lyons, PD, Zentil, PP & Wechsler, R 2018, 'Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results', Epilepsia. https://doi.org/10.1111/epi.14477
Szaflarski, Jerzy P. ; Bebin, Elizabeth Martina ; Comi, Anne M. ; Patel, Anup D. ; Joshi, Charuta ; Checketts, Daniel ; Beal, Jules C. ; Laux, Linda C. ; De Boer, Lisa M. ; Wong, Matthew H. ; Lopez, Merrick ; Devinsky, Orrin ; Lyons, Paul D. ; Zentil, Pilar Pichon ; Wechsler, Robert. / Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies : Expanded access program results. In: Epilepsia. 2018.
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T2 - Expanded access program results

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

PY - 2018/1/1

Y1 - 2018/1/1

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 - Tolerability

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