Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis

Table 1 Characteristics of the included studies in the meta-analysis

Study	Patients		Intervention	Comparison	Therapy duration	Inclusion criteria	Outcomes measures	Follow-up	Sample locations
Study	Number	Age (years)	Intervention	Comparison	Therapy duration	Inclusion criteria	Outcomes measures	Follow-up	Sample locations
Franz 2013 [24] NCT00789828	78:39	0–65	Everolimus (orally, starting dose 4.5 mg/m² per day)^a	Placebo	6 months	TSC with one target SEGA (≥1 cm³)	The tumor response	4–5 years	Multicenter
Bissler 2013 [25] NCT00790400	79:39	18–61	Everolimus (orally 10 mg per day)	Placebo	6 months	TSC with at least one AML (≥3 cm³)	AML tumor volume response	4–5 years	Multicenter
French 2016 [21] NCT01713946	119:117:130	2–65	Everolimus (orally 3–9 mg/m² per day) ^b	Placebo	26 weeks	TSC and therapy-resistant seizures	Response rate of seizure frequency	1 years	Multicenter
Krurger 2017 [26] NCT01289912	32:15	6–21	Everolimus (orally 4.5 mg/m² per day)	Placebo	6 months	TSC with a baseline verbal, performance or overall IQ score ≥ 60	TAND features	1 months	Two-center
Overwater 2016 [22] NTR3178	23:23	1.8–10.9	Sirolimus (orally, starting dose 1 mg/mL)^c	Crossover design	6 months	TSC with at least 1 epileptic seizure per week and resistant to at least 2 AEDs	Response rate in seizure frequency	6 months	The Netherlands

TSC tuberous sclerosis complex, SEGA subependymal giant cell astrocytoma; response in tumor volume, (a ≥ 50% reduction relative to the baseline in SEGA or AML); response rate (the proportion of patients achieving a ≥ 50% reduction relative to the baseline in seizure frequency)
^a Orally, at a starting dose of 4.5 mg/m² per day, subsequently adjusted to attain blood trough concentrations of 5–15 ng/mL
^b For patients younger than 10 years, the starting dose of everolimus was 6 mg/m² per day for those not receiving CYP3A4/PgP inducers and 9 mg/m² per day for those receiving CYP3A4/PgP inducers; for patients aged 10–18 years, the equivalent doses were 5 mg/m² per day and 8 mg/m² per day, respectively, and for those older than 18 years, they were 3 mg/m² per day and 5 mg/m² per day, respectively [21]
^c Starting from 1 mg/mL sirolimus orally, the dose was adjusted based on body weight and blood trough levels

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