We thank Drs. Zou and Liu for the comment on our article, [1] and for alerting us to an interesting Chinese study. [2] In the open-label uncontrolled study of 52 young children with TSC, 56% of participants showed a seizure response of 50% or more on treatment with sirolimus. [2] This effect size is in line with, but larger than, the effect size in our study and that of Krueger et al. [1,3] This may be due to the younger age of the participants, but is difficult to assess. Without a control group, further conclusions regarding effectiveness remain uncertain. The results of the EXIST-3 study recently showed a statistically significant effect of everolimus on seizure control in a large group of 366 patients with a response rate of up to 40% of participants (children under the age of two years were not included). [4] From the combination of these studies, a positive-effect pattern emerges of both rapalogs on intractable epilepsy, with an effect size that our study underpowered to detect. We agree that it is very important to investigate which patients may benefit from these therapies and at what point of treatment therapies will be most beneficial.
1. Overwater IE, Rietman AB, Bindels-de Heus K, et al. Sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized controlled trial. Neurology 2016;87:1011-1018.
2. Zou L, Liu Y, Pang L, et al. [Efficacy and safety of rapamycin in treatment of children with epilepsy complicated with tuberous sclerosis]. Zhonghua Er Ke Za Zhi 2014;52:812-816.
3. Krueger DA, Wilfong AA, Holland-Bouley K, et al. Everolimus treatment of refractory epilepsy in tuberous sclerosis complex. Ann Neuro. 2013;74:679-687.
4. French JA, Lawson JA, Yapici Z, et al. Adjunctive everolimus therapy for treatment-resistant focal- onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet Epub 2016 Sep 6.
For disclosures, please contact the editorial office at journal@neurology.org.
We thank Drs. Zou and Liu for the comment on our article, [1] and for alerting us to an interesting Chinese study. [2] In the open-label uncontrolled study of 52 young children with TSC, 56% of participants showed a seizure response of 50% or more on treatment with sirolimus. [2] This effect size is in line with, but larger than, the effect size in our study and that of Krueger et al. [1,3] This may be due to the younger age of the participants, but is difficult to assess. Without a control group, further conclusions regarding effectiveness remain uncertain. The results of the EXIST-3 study recently showed a statistically significant effect of everolimus on seizure control in a large group of 366 patients with a response rate of up to 40% of participants (children under the age of two years were not included). [4] From the combination of these studies, a positive-effect pattern emerges of both rapalogs on intractable epilepsy, with an effect size that our study underpowered to detect. We agree that it is very important to investigate which patients may benefit from these therapies and at what point of treatment therapies will be most beneficial.
1. Overwater IE, Rietman AB, Bindels-de Heus K, et al. Sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized controlled trial. Neurology 2016;87:1011-1018.
2. Zou L, Liu Y, Pang L, et al. [Efficacy and safety of rapamycin in treatment of children with epilepsy complicated with tuberous sclerosis]. Zhonghua Er Ke Za Zhi 2014;52:812-816.
3. Krueger DA, Wilfong AA, Holland-Bouley K, et al. Everolimus treatment of refractory epilepsy in tuberous sclerosis complex. Ann Neuro. 2013;74:679-687.
4. French JA, Lawson JA, Yapici Z, et al. Adjunctive everolimus therapy for treatment-resistant focal- onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet Epub 2016 Sep 6.
For disclosures, please contact the editorial office at journal@neurology.org.