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Randomized Controlled Trial
. 2021 Oct;62(10):2505-2517.
doi: 10.1111/epi.17036. Epub 2021 Aug 18.

Add-on cannabidiol in patients with Dravet syndrome: Results of a long-term open-label extension trial

Ingrid E Scheffer  1 , Jonathan J Halford  2 , Ian Miller  3 , Rima Nabbout  4 , Rocio Sanchez-Carpintero  5 , Yael Shiloh-Malawsky  6 , Matthew Wong  7 , Marta Zolnowska  8 , Daniel Checketts  9 , Eduardo Dunayevich  10 , Orrin Devinsky  11
Affiliations
Randomized Controlled Trial

Add-on cannabidiol in patients with Dravet syndrome: Results of a long-term open-label extension trial

Ingrid E Scheffer et al. Epilepsia. 2021 Oct.

Abstract

Objective: Add-on cannabidiol (CBD) reduced seizures associated with Dravet syndrome (DS) in two randomized, double-blind, placebo-controlled trials: GWPCARE1 Part B (NCT02091375) and GWPCARE2 (NCT02224703). Patients who completed GWPCARE1 Part A (NCT02091206) or Part B, or GWPCARE2, were enrolled in a long-term open-label extension trial, GWPCARE5 (NCT02224573). We present an interim analysis of the safety, efficacy, and patient-reported outcomes from GWPCARE5.

Methods: Patients received a pharmaceutical formulation of highly purified CBD in oral solution (100 mg/ml), titrated from 2.5 to 20 mg/kg/day over a 2-week period, added to their existing medications. Based on response and tolerance, CBD could be reduced or increased to 30 mg/kg/day.

Results: Of the 330 patients who completed the original randomized trials, 315 (95%) enrolled in this open-label extension. Median treatment duration was 444 days (range = 18-1535), with a mean modal dose of 22 mg/kg/day; patients received a median of three concomitant antiseizure medications. Adverse events (AEs) occurred in 97% patients (mild, 23%; moderate, 50%; severe, 25%). Commonly reported AEs were diarrhea (43%), pyrexia (39%), decreased appetite (31%), and somnolence (28%). Twenty-eight (9%) patients discontinued due to AEs. Sixty-nine (22%) patients had liver transaminase elevations >3 × upper limit of normal; 84% were on concomitant valproic acid. In patients from GWPCARE1 Part B and GWPCARE2, the median reduction from baseline in monthly seizure frequency assessed in 12-week periods up to Week 156 was 45%-74% for convulsive seizures and 49%-84% for total seizures. Across all visit windows, ≥83% patients/caregivers completing a Subject/Caregiver Global Impression of Change scale reported improvement in overall condition.

Significance: We show that long-term CBD treatment had an acceptable safety profile and led to sustained, clinically meaningful reductions in seizure frequency in patients with treatment-resistant DS.

Keywords: Dravet syndrome; antiseizure medication; cannabinoid; childhood onset epilepsy; convulsive seizures.

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References

REFERENCES

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