Long-Term Use of Cannabidiol (Epidiolex) in Patients with Refractory Epilepsy - The UW Health Experience
Abstract number :
2.235
Submission category :
7. Anti-seizure Medications / 7D. Drug Side Effects
Year :
2021
Submission ID :
1826361
Source :
www.aesnet.org
Presentation date :
12/5/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:53 AM
Authors :
Darina Georgieva, BS - University of Wisconsin School of Pharmacy; James Langley, PharmD - Clinical Pharmacist, Specialty Pharmacy, UW Health; Katherine Hartkopf, PharmD - Clinical Pharmacist, Specialty Pharmacy, UW Health; Lisa Hawk, PharmD - Clinical Pharmacist, Pharmacy, UW Health; Amanda Margolis, PharmD - Assistant Professor, Pharmacy Practice, University of Wisconsin School of Pharmacy; Barry Gidal, PharmD - Professor, Pharmacy Practice, University of Wisconsin School of Pharmacy
Rationale: Purified Cannabidiol, Epidiolex (CBD) is FDA approved for seizures associated with LGS, Dravet, and TSC. Phase III studies suggest that certain adverse effects (AEs) and/or PK/PD interactions may be therapy-limiting in some patients. Phase III studies are limited in duration, and open-label extension (OLE) studies tend to include a select population. This evaluation sought to characterize patients taking Epidiolex, identify factors that contribute to treatment success, as well as potential risk factors for treatment failure following long-term use.
Methods: A retrospective review of patients with refractory epilepsy taking CBD between December 2018 and December 2020 was performed. Inclusion criteria were established care with UW Health Neurology and at least one prescription fill of CBD at UW Health Specialty Pharmacy. Data collected included demographics, response to therapy, dosing, AEs, and concomitant antiseizure medications. Data is presented as mean (SD). Kaplan-Meier analysis was performed to describe CBD retention, as a measure of overall effectiveness.
Results: A total of 112 patients were screened; 4 were excluded due to lost follow-up or never starting CBD. Patient specific data are shown in Table 1. Of 108 patients, mean age was 20.3 years (13.1, range 2-63) and 52.8% female. Mean initial and maintenance doses were 5.3 mg/kg/d (1.3) and 15.3 mg/kg/d (5.8), respectively. As of April 2021, 75% of patients remained on CBD, 23% had d/c, and 1.9% had d/c and then re-started. Treatment retention over time is displayed in Figure 1. The 25th percentile for d/c was 19 months. Reasons for discontinuation (d/c) are listed in Table 1. 46.3% of patients experienced at least one treatment emergent adverse effects (TEAE) with 14.5% d/c CBD due to TEAE. Most common reasons for d/c were lack of efficacy (37%), increased seizure activity (22%), worsened behavior (22%), and sedation (22%). Of patients with available lab values, 5.9% presented with AST > 3X ULN at 1 month 8.3% at 2 months and 0% at month 3 following CBD initiation. 1 out of 27 d/c were due to LFT elevations (3.7%). Increased seizure activity was seen in 5.56% of total patients and 22.2% of the patients who ultimately d/c CBD. At the time of starting CBD, 47.2% were concurrently taking clobazam, 39.2% of those patients had a clobazam dose decrease around the same time. 53% of patients were able to either discontinue or lower the dose of at least one other antiseizure medication.
Conclusions: Our data is similar to Phase III and OLE studies in patients with intractable, rare epilepsies. CBD is generally well-tolerated and the majority continued long-term treatment. With patterns of AEs being similar to clinical trials. However, GI complaints, such as diarrhea, and significant LFT elevations were less common. Our data suggest most d/c occur within the first several months of treatment. Further studies designed to evaluate early identification and potential mitigation of AEs, including drug interactions, are ongoing.
Funding: Please list any funding that was received in support of this abstract.: None.
Anti-seizure Medications