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Advanced Neurology mTOR inhibition in epilepsy

Table 2. (Continued)
Authors Study design Disease of primary n Age (y) a Durationa Seizure outcomeb Other findings
interest
Krueger et al. 109 Open-labeled TSC with refractory 14 8 (2 – 21.3) 48 m Responders in 93% AE grade 1 – 2 in
extension of Krueger epilepsy of pts 94% of pts (72.5%
et al. 67 of reported AE
were Rx-related
and 2%
serious AE)
Samueli et al. 110 Prospective, TSC with refractory 15 6 (1 – 18) median 22 m (6 Responders in 80% of Transient AE in
open-labeled epilepsy – 50) pts (58% sz free) 93% of pts. None
withdrew due
to AE.
French et al. 69 Phase 3, prospective, TSC with refractory 366 10.1 (2.2 – 56.3) 18 w (6 w Responders: Serious AE (Rx
double-blind, epilepsy titration, 12 w 15.1% in the placebo withdrawal):
placebo-controlled maintenance) group 3% of pts (2%) in
(EXIST-3) 28.2% in LE placebo
40% in HE 14% (5%) in LE
14% (3%) in LE
Franz et al. 64 Open-labeled TSC with refractory 361 10 21 m (2 – 165) Responders in 31% of AE grade 3 – 4 in
extension of EXIST-3 epilepsy pts at 18 w, 46.6% at 40.2% of pts; 13%
1 y, and 57.7% at 2 y withdrew due
to AE; 2 deaths
were Rx-related
(pneumonia,
septic shock)
Curatolo Post hoc study of TSC with refractory 299 4.1 (2.2 – 5.9) 18 w (6 w Responders aged <6 y AE grade 3 – 4
et al. 71 EXIST-3 epilepsy titration, 12 w (≥6 y): reported in:
maintenance) 17.6% (12.9%) in 45% of pts
placebo group aged <6 y
30.3% (27%) in LE 38% of pts
59.5% (30%) in HE aged ≥6 y
Mizuguchi Sub-study of TSC with refractory 35 8.8 (2.9 – 16.6) 18 w (6 w Responders: 36.4% of pts with
et al. 111 EXIST-3 epilepsy titration, 12 w 0% in the placebo ASD in the Rx
maintenance) group group and 12.5%
30% in LE in the placebo
28.6% in HE group showed
PARS drop by
≥5 points.
Franz et al. 70 Open-labeled, TSC with refractory 244 9.7 (2.2 – 52.3) 48 w At 12 w: 18.9% sz free, 98.6% of pts had
post-extension of epilepsy 64.8% improved sz AE; AE grade
EXIST-3 At 24 w: 18.2% Sz free, 3 – 4 in 45.2%
64.5% improved sz of pts; 13.9%
At 36 w: 17.1% sz free, withdrew Rx due
70.1% improved sz, to AE.
At 48 w: 20% sz free,
61.8% improved sz.
Stockinger Retrospective chart TSC with refractory 45 31.6±11 42±28 m Responders in 33% of 42.2% of pts had
et al. 112 review epilepsy pts (4 had sz free) AE; serious AE in
13.3%.
Notes: Age and duration were expressed in median years (range) or mean±SD, unless indicated otherwise; Responders were referred to those with
a
b
seizure reduction of at least 50%.
Abbreviations: AE: Adverse events; ASD: Autism spectrum disorder; EXIST: Examining everolimus in a study of tuberous sclerosis complex trial;
GI: Gastrointestinal; HE: High everolimus exposure group with a blood trough target of 9 – 15 ng/mL; LE: Low everolimus exposure group with a
blood trough target of 3 – 7 ng/mL; PARS: Pervasive developmental disorders autism society Japan rating scale; pts: Patients; Rx: Treatment;
SEGA: Subependymal giant cell astrocytoma; sz: Seizure; TSC: Tuberous sclerosis complex; m: Month (s); w: Week (s); y: Year (s).

Volume 3 Issue 3 (2024) 10 doi: 10.36922/an.3568