Long‐term efficacy and safety of cannabidiol in patients with treatment‐resistant epilepsies: Four‐year results from the expanded access program

Szaflarski, Jerzy P.; Devinsky, Orrin; Lopez, Merrick; Park, Yong D.; Zentil, Pilar Pichon; Patel, Anup D.; Thiele, Elizabeth A.; Wechsler, Robert; Checketts, Daniel; Sahebkar, Farhad

doi:10.1111/epi.17496

Cited by 17 publications

(19 citation statements)

References 27 publications

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“…[8][9][10][11][12] In the final pooled analysis of 892 patients treated through January 2019 (median treatment duration = 694 days [range = 10-1793]), CBD treatment was associated with 50%-67% and 46%-66% reductions in median monthly convulsive and total seizure frequency, respectively. 13 CBD was generally well tolerated in the EAP, and treatmentemergent adverse events (AEs) were similar to those reported in the RCTs. [3][4][5][6][7][8][9][10][11][12] Previous EAP analyses have largely focused on a general assessment of seizures in TRE or seizures associated with LGS, DS, or TSC, rather than individual seizure types.…”

Section: Introductionmentioning

confidence: 57%

“…Baseline characteristics had been reported previously. 13 Briefly, median age was 12 years (range = 0-75), and patients were taking a median of 3 (range = 0-10) concurrent ASMs. The most commonly used ASMs were clobazam (48%), levetiracetam (34%), and valproate (28%).…”

Section: Patientsmentioning

confidence: 99%

“…Safety was assessed for up to 252 weeks, and results have been reported previously. 13 AEs were reported in 88% of patients (788/892) and led to CBD discontinuation in 7% of patients (65/892). AEs reported in >20% of patients included diarrhea (33%, 298/892), seizure (24%, 210/892), and somnolence (23%, 202/892).…”

Section: Safetymentioning

confidence: 99%

“…[3][4][5][6][7][8][9][10][11][12] Previous EAP analyses have largely focused on a general assessment of seizures in TRE or seizures associated with LGS, DS, or TSC, rather than individual seizure types. [9][10][11][12][13] However, CBD (Epidiolex) is frequently used off-label for seizures other than those associated with the approved conditions. Such use is partially supported by results from a systematic review and an earlier smaller EAP analysis, which suggested efficacy in a broad range of seizure types, including treatment-resistant absence seizures and epileptic spasms.…”

Section: Introductionmentioning

confidence: 99%

“…Efficacy data were analyzed descriptively. Safety data were assessed for the full duration of the follow-up (up to 252 weeks) and are reported separately 13 ; a brief overview is presented here.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of cannabidiol in convulsive and nonconvulsive seizure types associated with treatment‐resistant epilepsies in the Expanded Access Program

Flamini¹,

Comi

Peters

et al. 2023

Epilepsia

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The cannabidiol (CBD) Expanded Access Program (EAP), initiated in 2014, provided CBD (Epidiolex) to patients with treatment‐resistant epilepsy (TRE). In the final pooled analysis of 892 patients treated through January 2019 (median exposure = 694 days), CBD treatment was associated with a 46%–66% reduction in median monthly total (convulsive plus nonconvulsive) seizure frequency. CBD was well tolerated, and adverse events were consistent with previous findings. We used pooled EAP data to investigate the effectiveness of add‐on CBD therapy for individual convulsive seizure types (clonic, tonic, tonic–clonic, atonic, focal to bilateral tonic–clonic), nonconvulsive seizure types (focal with and without impaired consciousness, absence [typical and atypical], myoclonic, myoclonic absence), and epileptic spasms. CBD treatment was associated with a reduction in the frequency of convulsive seizure types (median percentage reduction = 47%–100%), and nonconvulsive seizure types and epileptic spasms (median percentage reduction = 50%–100%) across visit intervals through 144 weeks of treatment. Approximately 50% of patients had ≥50% reduction in convulsive and nonconvulsive seizure types and epileptic spasms at nearly all intervals. These results show a favorable effect of long‐term CBD use in patients with TRE, who may experience various convulsive and nonconvulsive seizure types. Future controlled trials are needed to confirm these findings.

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Section: Introductionmentioning

confidence: 57%

Section: Patientsmentioning

confidence: 99%

Section: Safetymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy of cannabidiol in convulsive and nonconvulsive seizure types associated with treatment‐resistant epilepsies in the Expanded Access Program

Flamini¹,

Comi

Peters

et al. 2023

Epilepsia

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Final analysis of potential drug–drug interactions between highly purified cannabidiol and anti‐seizure medications in an open‐label expanded access program

Gaston,

Bebin,

Cutter

et al. 2023

Epilepsia Open

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ObjectiveThe aim of this study was to assess for potential drug‐drug interactions between highly purified cannabidiol (CBD) and anti‐seizure medications (ASMs).MethodsOur group previously reported that in a sample of adults and children receiving CBD in an open label expanded access program, there were several ASMs noted to increase in serum level with increasing doses of CBD. We analyzed if an increased number of observations over time resulted in changes in potential interactions and if potential interactions were associated with time since enrollment, demographics, or overall rating of adverse effects.ResultsIn 169 participants (80 adults), with increasing weight‐based CBD dose, there were associated increases in serum levels of clobazam and N‐desmethylclobazam, free valproate, felbamate, and topiramate in adult and pediatric arms combined, levetiracetam in the pediatric arm only, and permapanel in the adult arm only. There were no associations noted in these level changes with time since enrollment, biological sex, and Adverse Events Profile scores.SignificanceThis study confirms some previously identified interactions with CBD and identifies other potential pharmacokinetic interactions; however, the clinical significance of these observations is likely minor and there is no effect of time on these findings.

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Long‐term efficacy and safety of cannabidiol in patients with tuberous sclerosis complex: 3‐year results from the cannabidiol expanded access program

Weinstock,

Bebin,

Checketts

et al. 2024

Epilepsia Open

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ObjectiveThe cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment‐resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long‐term efficacy and safety outcomes for add‐on CBD treatment in patients with TSC.MethodsPatients received plant‐derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25–50 mg/kg/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and ≥ 50%, ≥75%, and 100% responder rates across 12‐week visit windows through 144 weeks. Adverse events (AEs) are reported through 233 weeks.ResultsThirty‐four patients with confirmed TSC were included. Mean age was 12.4 years (range, 1.8–31.2), and patients were receiving a median of 3 (range, 1–7) antiseizure medications (ASMs) at baseline. Median CBD dose was 25–28 mg/kg/d for 36 weeks and then 20–50 mg/kg/d through 228 weeks. Dose reduction from baseline occurred for most ASMs, except topiramate. Median reduction in the frequency of convulsive, focal, and total seizures was 44%–81%, 51%–87%, and 44%–87%, respectively, through 144 weeks. Responder rates (≥50%, ≥75%, and 100% reduction) were 43%–71%, 14%–58%, and 0%–25% for convulsive seizures; 52%–75%, 35%–60%, and 7%–32% for focal seizures; and 46%–79%, 26%–65%, and 0%–13% for total seizures. A total of 94% of patients experienced ≥1 AE; 47% had serious AEs, considered treatment unrelated by the investigator. Treatment‐related AEs (TRAEs) occurred in 71% of patients. The most frequently reported TRAEs were somnolence, diarrhea, and ataxia. Two patients experienced AEs leading to discontinuation. There were no deaths.SignificanceLong‐term add‐on CBD use was associated with reduced seizure frequency through 144 weeks. The safety profile was consistent with previous reports.Plain Language SummaryIn this study, we evaluated efficacy and safety of cannabidiol (CBD) treatment in patients with tuberous sclerosis complex receiving CBD in addition to other antiseizure treatments in an Expanded Access Program. After starting CBD, 46%–79% of patients had at least 50% reduction and 26%–65% had at least 75% reduction in the number of seizures per month; up to 13% had no seizures through 144 weeks. Safety results were similar to prior studies; sleepiness and diarrhea were common treatment‐related side effects. These results show that long‐term CBD treatment was associated with fewer seizures and mild/moderate side effects.

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Long‐term efficacy and safety of cannabidiol in patients with treatment‐resistant epilepsies: Four‐year results from the expanded access program

Cited by 17 publications

References 27 publications

Efficacy of cannabidiol in convulsive and nonconvulsive seizure types associated with treatment‐resistant epilepsies in the Expanded Access Program

Efficacy of cannabidiol in convulsive and nonconvulsive seizure types associated with treatment‐resistant epilepsies in the Expanded Access Program

Final analysis of potential drug–drug interactions between highly purified cannabidiol and anti‐seizure medications in an open‐label expanded access program

Long‐term efficacy and safety of cannabidiol in patients with tuberous sclerosis complex: 3‐year results from the cannabidiol expanded access program

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