Table 2.
Efficacy of pharmacotherapies from the pivotal RCTs and OLE studies for TSC-associated epilepsy.
| Study design | Patient characteristics | Interventions + comparator | Median baseline monthly TSC-associated seizure frequency | Median percent reduction in TSC-associated seizure; p-value versus PBO | ⩾ 50% responder rate; p value versus PBO | Improvement in overall condition/behaviour/QoL | |
|---|---|---|---|---|---|---|---|
| EVE: EXIST-371,74 | Phase III RCT 18 wks |
• Median (range) age: 10.1 (2.2–56.3) y • Failed >6 prior ASDs: 39% |
EVE-LT (n = 117) | Per week: 8.6 (range: 1.4–192.9) | 29.3% (95% CI 18.8–41.9); p = 0.0028 |
28.2% (95% CI 20.3–37.3); p = 0.0077 | Mean (SD) change in QOLCE total score Responders: 5:8 (11.0); p = 0.016 versus non-responders Non-responders: 1.7 (10.7) Mean (SD) change in QOLIE-AD-48 total score: Responders: 8.2 (12.4); p = 0.155 Non-responders: 2.6 (10.7) Mean (SD) change in QOLIE-31-P total score Responders: 15.2 (15.7); p = 0.021 Non-responders: -0.6 (15.3) |
| EVE-HT (n = 130) | 9.5 (0.3–218.4) | 39.6% (35.0–48.7); p < 0.0001 |
40.0% (31.5–49.0); p < 0.0001 | ||||
| PBO (n = 119) | 10.5 (1.3–231.7) | 14.9% (0.1–21.7) | 15.1% (9.2–22.8) | ||||
| EVE: EXIST-3 OLE 75 | OLE: 48 mo (2 y) | • Median (range) age: 10.03 (2.2–56.3) y | EVE (target exposure, 3–15 ng/mL) (n = 361) | NR | 31.7% (28.5–36.1), 46.7% (40.2–54), 56.9% (50–68.4) at 18 wk, 1 y and 2 y, respectively | 31% (26.2–36.1), 46.6% (40.9–52.5), 57.7% (49.7–65.4) at 18 wk, 1 y and 2 y, respectively |
NR |
| CBD: GWPCARE676 | Phase III RCT 16 wks: 4-wk titration and 12-wk maintenance phase. | • Median (range) age: 11.4 (1.1–56.8) y • Median current ASDs: 3 • Median prior ASDs: 4 |
CBD25 (n = 75) | Per 28 days: 56.0 (IQR: 21.2–101.0) |
48.6% (40.4–55.8); p < 0.00 | 36%; p = 0.07 | Percentage with improvement in overall condition S/CGIC 69%; OR = 2.25; p = 0.0074 |
| CBD50 (n = 73) | 61.0 (36.0–117.0) | 47.5% (39.0–54.8); p = 0.002 | 40%; p = 0.02 | 62%; OR = 1.77; p = 0.0580 | |||
| PBO (n = 76) | 54.1 (26.4–102.0) | 26.5% (14.9–36.5) | 22% | 40% | |||
| CBD: GWPCARE6 OLE 77 | OLE: 48 wks | Median (range) age: 10.8 (1.1–56.8) y | CBD25 with titration up to CBD50 (n = 199) | 56.9 (28.0– 109.0) | 12-wk windows over 48 wks: 54–68% | Wk 1-12: 53% Wk 13–24: 53% Wk 25–36: 58% Wk 37–48: 61% |
S/CGIC: 87% of patients/caregivers at wk 26 P/GIC: 80% of physicians at wk 26 |
ASD, anti-seizure drug; CBD, cannabidiol; CBD25, CBD 25 mg/kg/day; CBD50, CBD 50 mg/kg/day; CI, confidence interval; EVE, everolimus; IQR, interquartile range; HT, high trough (range of 9–15 ng/ml); LT, low trough (range of 3–7 ng/ml); mo, months; NR, not reported; OLE, open-label extension trial; OR, adds ratio; PBO, placebo; P/GIC, Physician Global Impression of Change; QoL, quality of life; QOLCE, Quality of Life in Childhood Epilepsy Questionnaire; QOLIE-AD-48, Quality of Life in Epilepsy Inventory-Adolescents-48; QOLIE-31-P, Patient Weighted Quality of Life in Epilepsy Inventory-Form 31; RCT, randomised controlled trial; S/CGIC, Subject/Caregiver Global Impression of Change; SD, standard deviation; wk, week; y, year(s).