Abstract
Background
Tuberous sclerosis complex is a genetic disease usually caused by mutations to either
TSC1 or TSC2, where its gene products are involved in the inhibition of the mammalian target of
rapamycin pathway. Under normal cellular conditions, mammalian target of rapamycin
(mTOR) regulates cell growth and proliferation in response to signals from nutrients
or growth factors, but loss of TSC1 or TSC2 leads to overactivation of mTOR and uncontrolled cellular proliferation. Everolimus
is an mTOR inhibitor approved for use in a number of indications where mTOR overactivation
is implicated, including tuberous sclerosis complex.
Methods and patients
We conducted a literature search of PubMed to identify published articles about the
long-term efficacy and safety of everolimus in patients with tuberous sclerosis complex.
Results
The short-term efficacy and safety of everolimus in patients with tuberous sclerosis
complex has been demonstrated in placebo-controlled trials, and open-label extension
studies are ongoing to monitor long-term effects, including safety. Examples of regrowth
following discontinuation of mTOR inhibitors suggest that everolimus needs to be given
indefinitely to maintain suppression of subependymal giant cell astrocytoma and other
tuberous sclerosis complex–associated disease manifestations. No additional safety
concerns have been reported to date with long-term administration of everolimus, but
published long-term data (>1 year treatment) are currently limited to a small open-label
trial and case reports for this relatively rare condition.
Conclusions
From the limited data available, long-term administration of everolimus appears feasible
with few safety concerns beyond those associated with short-term use. Further investigation
is needed to determine the long-term efficacy and safety of everolimus in patients
with tuberous sclerosis complex.
Keywords
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Article info
Publication history
Published online: November 07, 2014
Accepted:
October 26,
2014
Received:
July 30,
2014
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
