Authors :
Presenting Author: Sarah Wilson, MD – McGovern Medical School
Mary Kay Koenig, MD – McGovern Medical School; Debopam Samanta, MD – University of Arkansas for Medical Sciences; Darcy A. Krueger, MD, PhD – Cincinnati Children's Hospital Medical Center; Shelly Meitzler, AA – TSC Alliance; Carly Kaye, MEd – TSC Alliance; Sherry R. Danese, MBA – Outcomes Insights; Timothy B. Saurer, PhD – Jazz Pharmaceuticals; Kelly C. Simontacchi, PhD – Jazz Pharmaceuticals; Karthik Rajasekaran, PhD – Jazz Pharmaceuticals
Rationale: More than 90% of people with TSC have TSC-associated neuropsychiatric disorders (TAND), characterized by cognitive, behavioral, and psychiatric symptoms. A pharmaceutical formulation of highly purified CBD is approved for the treatment of seizures associated with TSC. BECOME-TSC (caregiver survey to assess changes in BEhavior, COgnition, and More with Epidiolex® in TSC) is an ongoing cross-sectional survey to quantify the real-world impact of CBD treatment on seizure and nonseizure outcomes in people with TSC. Here we report preliminary findings on nonseizure outcomes of the survey.
Methods: Using electronic health records, healthcare providers at TSC centers identified people with TSC who were treated with CBD (Epidiolex®, 100 mg/kg oral solution) for ≥ six months. Caregivers of these patients completed an online survey, consisting of multiple choice and rank order questions, based on the TAND questionnaire, other validated measures, and previous caregiver reports, using a symmetrical Likert scale (from worsening to improvement). Continuous variables were summarized as means, medians, and ranges, and categorical variables as frequency distributions and percentages. CBD-associated AEs, which include transaminase elevations, somnolence, decreased appetite, diarrhea, pyrexia, vomiting, fatigue, rash, sleep disorders, and infections, were not assessed.
Results: At the time of this analysis, eight caregivers of patients with TSC had completed the survey. Mean (standard deviation [SD]) age of patients was 14 (nine) y, and 50% were female. The mean (SD) age at seizure onset was eight (seven) months, and 63% of patients had a history of infantile spasms. The median CBD dose was 16 mg/kg/d. The most common concomitant ASMs were everolimus (50%), clonazepam (38%), and oxcarbazepine (38%). Patients were diagnosed with the following co-occurring conditions: developmental delay (88%), autism spectrum disorder (88%), attention deficit hyperactivity disorder (38%), and anxiety disorder (38%). Severe–profound intellectual disability (ID) was reported in 63% of patients, mild–moderate ID in 25%, and 13% of patients had fluent verbal language. Compared with the period before CBD initiation, respondents most commonly reported definite improvements (for ≥ the past month) in a patient’s ability to shake head for yes/no answer (80%), accomplish visuo-spatial tasks (80%), be happy (75%), learn new things (71%), and be aware of surroundings (71%). Definite worsening was reported by ≤ 1 respondent in domains that included using repetitive words/phrases, repetitive behaviors, impulsivity, and overactivity/hyperactivity.
Conclusions: These preliminary results show that a substantial proportion of caregivers of people with TSC reported improvement in TAND-related outcomes since initiating CBD. A total of 88% of caregivers reported planning to continue CBD, with reduced seizure frequency, reduced seizure severity/duration, and improved cognition as the most common reasons for continuation.
Funding: Jazz Pharmaceuticals Inc.