Long-term safety and efficacy of cannabidiol in children and adults with treatmentresistant Lennox-Gastaut syndrome or Dravet syndrome

Expanded access program results

Linda C Laux*, E. Martina Bebin, Daniel Checketts, Michael Chez, Robert Flamini, Eric D. Marsh, Ian Miller, Kathryn Nichol, Yong Park, Eric Segal, Laurie Seltzer, Jerzy P. Szaflarski, Elizabeth A. Thiele, Arie Weinstock

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016. Methods: Children and adults with LGS/DS taking stable doses of antiepileptic drugs (AEDs) at baseline were included from 25 EAP sites across the United States. During the 4-week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received a pharmaceutical formulation of highly purified CBD (Epidiolex®; 100 mg/mL) in oral solution at 2–10 mg/kg/day, titrated until tolerability limit or a maximum dose of 25–50 mg/kg/day. Patient visits were every 2–4 weeks. The percentage change from baseline in median monthly convulsive (ie, major motor) and total seizures was evaluated at 12-week intervals through 96 weeks. The percentages of patients who had ≥50%, ≥75%, and 100% reduction in monthly seizures relative to the baseline period were also evaluated. Adverse events (AEs) were monitored and summarized for the safety analysis set (SAS) through 144 weeks. Results: Of the 607 patients in the SAS, 58 had DS and 94 had LGS (N = 152); 455 patients had other TREs. Twenty-eight percent of LGS/DS patients withdrew, primarily owing to lack of efficacy (20%). LGS/DS patients were taking a median of 3 (0–10) concomitant AEDs. Median treatment duration was 78.3 (range, 4.1–146.4) weeks. Between weeks 12 and 96, median CBD dose ranged from 21 to 25 mg/kg/day. At 12 weeks, add-on CBD reduced median monthly major motor seizures by 50% and total seizures by 44%, with consistent reductions in both seizure types through 96 weeks. At 12 weeks, the proportions of patients with ≥50%, ≥75%, and 100% reductions in major motor seizures were 53%, 23%, and 6%; the proportions with corresponding reductions in total seizures were 46%, 26%, and 5%. Responder rates for both seizure types were consistent through 96 weeks. CBD had an acceptable safety profile; the most common AEs were somnolence (30%) and diarrhea (24%). Conclusions: Results from this interim analysis support add-on CBD as an effective long-term treatment option in LGS or DS.

Original languageEnglish (US)
Pages (from-to)13-20
Number of pages8
JournalEpilepsy Research
Volume154
DOIs
StatePublished - Aug 1 2019

Fingerprint

Cannabidiol
Myoclonic Epilepsy
Seizures
Safety
Anticonvulsants
Epilepsy
Therapeutics
Lennox Gastaut Syndrome
Drug Compounding
Patient Safety
Caregivers
Diarrhea
Parents

Keywords

  • Cannabidiol
  • Dravet syndrome
  • Efficacy
  • Expanded access program
  • Lennox-Gastaut syndrome
  • Seizures
  • Tolerability
  • Treatment-resistant epilepsy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Laux, Linda C ; Bebin, E. Martina ; Checketts, Daniel ; Chez, Michael ; Flamini, Robert ; Marsh, Eric D. ; Miller, Ian ; Nichol, Kathryn ; Park, Yong ; Segal, Eric ; Seltzer, Laurie ; Szaflarski, Jerzy P. ; Thiele, Elizabeth A. ; Weinstock, Arie. / Long-term safety and efficacy of cannabidiol in children and adults with treatmentresistant Lennox-Gastaut syndrome or Dravet syndrome : Expanded access program results. In: Epilepsy Research. 2019 ; Vol. 154. pp. 13-20.
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abstract = "Background: Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016. Methods: Children and adults with LGS/DS taking stable doses of antiepileptic drugs (AEDs) at baseline were included from 25 EAP sites across the United States. During the 4-week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received a pharmaceutical formulation of highly purified CBD (Epidiolex{\circledR}; 100 mg/mL) in oral solution at 2–10 mg/kg/day, titrated until tolerability limit or a maximum dose of 25–50 mg/kg/day. Patient visits were every 2–4 weeks. The percentage change from baseline in median monthly convulsive (ie, major motor) and total seizures was evaluated at 12-week intervals through 96 weeks. The percentages of patients who had ≥50{\%}, ≥75{\%}, and 100{\%} reduction in monthly seizures relative to the baseline period were also evaluated. Adverse events (AEs) were monitored and summarized for the safety analysis set (SAS) through 144 weeks. Results: Of the 607 patients in the SAS, 58 had DS and 94 had LGS (N = 152); 455 patients had other TREs. Twenty-eight percent of LGS/DS patients withdrew, primarily owing to lack of efficacy (20{\%}). LGS/DS patients were taking a median of 3 (0–10) concomitant AEDs. Median treatment duration was 78.3 (range, 4.1–146.4) weeks. Between weeks 12 and 96, median CBD dose ranged from 21 to 25 mg/kg/day. At 12 weeks, add-on CBD reduced median monthly major motor seizures by 50{\%} and total seizures by 44{\%}, with consistent reductions in both seizure types through 96 weeks. At 12 weeks, the proportions of patients with ≥50{\%}, ≥75{\%}, and 100{\%} reductions in major motor seizures were 53{\%}, 23{\%}, and 6{\%}; the proportions with corresponding reductions in total seizures were 46{\%}, 26{\%}, and 5{\%}. Responder rates for both seizure types were consistent through 96 weeks. CBD had an acceptable safety profile; the most common AEs were somnolence (30{\%}) and diarrhea (24{\%}). Conclusions: Results from this interim analysis support add-on CBD as an effective long-term treatment option in LGS or DS.",
keywords = "Cannabidiol, Dravet syndrome, Efficacy, Expanded access program, Lennox-Gastaut syndrome, Seizures, Tolerability, Treatment-resistant epilepsy",
author = "Laux, {Linda C} and Bebin, {E. Martina} and Daniel Checketts and Michael Chez and Robert Flamini and Marsh, {Eric D.} and Ian Miller and Kathryn Nichol and Yong Park and Eric Segal and Laurie Seltzer and Szaflarski, {Jerzy P.} and Thiele, {Elizabeth A.} and Arie Weinstock",
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language = "English (US)",
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Laux, LC, Bebin, EM, Checketts, D, Chez, M, Flamini, R, Marsh, ED, Miller, I, Nichol, K, Park, Y, Segal, E, Seltzer, L, Szaflarski, JP, Thiele, EA & Weinstock, A 2019, 'Long-term safety and efficacy of cannabidiol in children and adults with treatmentresistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results', Epilepsy Research, vol. 154, pp. 13-20. https://doi.org/10.1016/j.eplepsyres.2019.03.015

Long-term safety and efficacy of cannabidiol in children and adults with treatmentresistant Lennox-Gastaut syndrome or Dravet syndrome : Expanded access program results. / Laux, Linda C; Bebin, E. Martina; Checketts, Daniel; Chez, Michael; Flamini, Robert; Marsh, Eric D.; Miller, Ian; Nichol, Kathryn; Park, Yong; Segal, Eric; Seltzer, Laurie; Szaflarski, Jerzy P.; Thiele, Elizabeth A.; Weinstock, Arie.

In: Epilepsy Research, Vol. 154, 01.08.2019, p. 13-20.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Long-term safety and efficacy of cannabidiol in children and adults with treatmentresistant Lennox-Gastaut syndrome or Dravet syndrome

T2 - Expanded access program results

AU - Laux, Linda C

AU - Bebin, E. Martina

AU - Checketts, Daniel

AU - Chez, Michael

AU - Flamini, Robert

AU - Marsh, Eric D.

AU - Miller, Ian

AU - Nichol, Kathryn

AU - Park, Yong

AU - Segal, Eric

AU - Seltzer, Laurie

AU - Szaflarski, Jerzy P.

AU - Thiele, Elizabeth A.

AU - Weinstock, Arie

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Background: Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016. Methods: Children and adults with LGS/DS taking stable doses of antiepileptic drugs (AEDs) at baseline were included from 25 EAP sites across the United States. During the 4-week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received a pharmaceutical formulation of highly purified CBD (Epidiolex®; 100 mg/mL) in oral solution at 2–10 mg/kg/day, titrated until tolerability limit or a maximum dose of 25–50 mg/kg/day. Patient visits were every 2–4 weeks. The percentage change from baseline in median monthly convulsive (ie, major motor) and total seizures was evaluated at 12-week intervals through 96 weeks. The percentages of patients who had ≥50%, ≥75%, and 100% reduction in monthly seizures relative to the baseline period were also evaluated. Adverse events (AEs) were monitored and summarized for the safety analysis set (SAS) through 144 weeks. Results: Of the 607 patients in the SAS, 58 had DS and 94 had LGS (N = 152); 455 patients had other TREs. Twenty-eight percent of LGS/DS patients withdrew, primarily owing to lack of efficacy (20%). LGS/DS patients were taking a median of 3 (0–10) concomitant AEDs. Median treatment duration was 78.3 (range, 4.1–146.4) weeks. Between weeks 12 and 96, median CBD dose ranged from 21 to 25 mg/kg/day. At 12 weeks, add-on CBD reduced median monthly major motor seizures by 50% and total seizures by 44%, with consistent reductions in both seizure types through 96 weeks. At 12 weeks, the proportions of patients with ≥50%, ≥75%, and 100% reductions in major motor seizures were 53%, 23%, and 6%; the proportions with corresponding reductions in total seizures were 46%, 26%, and 5%. Responder rates for both seizure types were consistent through 96 weeks. CBD had an acceptable safety profile; the most common AEs were somnolence (30%) and diarrhea (24%). Conclusions: Results from this interim analysis support add-on CBD as an effective long-term treatment option in LGS or DS.

AB - Background: Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016. Methods: Children and adults with LGS/DS taking stable doses of antiepileptic drugs (AEDs) at baseline were included from 25 EAP sites across the United States. During the 4-week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received a pharmaceutical formulation of highly purified CBD (Epidiolex®; 100 mg/mL) in oral solution at 2–10 mg/kg/day, titrated until tolerability limit or a maximum dose of 25–50 mg/kg/day. Patient visits were every 2–4 weeks. The percentage change from baseline in median monthly convulsive (ie, major motor) and total seizures was evaluated at 12-week intervals through 96 weeks. The percentages of patients who had ≥50%, ≥75%, and 100% reduction in monthly seizures relative to the baseline period were also evaluated. Adverse events (AEs) were monitored and summarized for the safety analysis set (SAS) through 144 weeks. Results: Of the 607 patients in the SAS, 58 had DS and 94 had LGS (N = 152); 455 patients had other TREs. Twenty-eight percent of LGS/DS patients withdrew, primarily owing to lack of efficacy (20%). LGS/DS patients were taking a median of 3 (0–10) concomitant AEDs. Median treatment duration was 78.3 (range, 4.1–146.4) weeks. Between weeks 12 and 96, median CBD dose ranged from 21 to 25 mg/kg/day. At 12 weeks, add-on CBD reduced median monthly major motor seizures by 50% and total seizures by 44%, with consistent reductions in both seizure types through 96 weeks. At 12 weeks, the proportions of patients with ≥50%, ≥75%, and 100% reductions in major motor seizures were 53%, 23%, and 6%; the proportions with corresponding reductions in total seizures were 46%, 26%, and 5%. Responder rates for both seizure types were consistent through 96 weeks. CBD had an acceptable safety profile; the most common AEs were somnolence (30%) and diarrhea (24%). Conclusions: Results from this interim analysis support add-on CBD as an effective long-term treatment option in LGS or DS.

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KW - Dravet syndrome

KW - Efficacy

KW - Expanded access program

KW - Lennox-Gastaut syndrome

KW - Seizures

KW - Tolerability

KW - Treatment-resistant epilepsy

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