Conference Coverage

Guidance coming for mTOR inhibitors in infantile TSC

Publish date: May 17, 2018

REPORTING FROM AAN 2018

LOS ANGELES – Someday soon, physicians will probably have solid, evidence-based guidelines on how to use mTOR inhibitors in infants with tuberous sclerosis complex.

They couldn’t come soon enough. Everolimus (Afinitor) is being used off label more and more often in children under 2 years old for seizures and other manifestations of the genetic disorder, often with a decent response.

^{M. Alexander Otto/MDedge News}

Dr. Darcy Krueger

But all the trials for everolimus and sirolimus (Rapamune), the other mTOR [mammalian target of rapamycin] inhibitor used in tuberous sclerosis complex (TSC), were done in older children and adults, so there’s uncertainty about using them in infants, and wide variation in how they’re used. Also, the few available case reports and series raise the possibility that side effects might be more common and perhaps serious in the very young, according to Darcy Krueger, MD, PhD, director of the Tuberous Sclerosis Clinic at Cincinnati Children’s Hospital.

“I get emails all the time saying ‘how would you start treatment at this age?’ and we say there are no data,” he said at the American Academy of Neurology annual meeting.

Dr. Krueger presented a survey of 19 TSC centers to get the ball rolling. They reported on treating 45 children under 2 years old, at least one child at each center. The goal of the survey was to establish a baseline “to allow us to move forward with what proper studies would look like, and what needs to be done. Two-thirds of patients have seizures before their first birthday; we need to establish a safety [and efficacy] profile well before 2 years of age,” and evidence-based guidelines, he said.

On average, everolimus treatment started at 11.7 months, and continued for 27 months. Sirolimus treatment started at a mean of 16 months and continued for 16 months. Dosing ranged from once a week to daily. In contrast to case reports that skew heavily toward rhabdomyomas, most of the children were treated for epilepsy and subependymal giant cell astrocytoma (SEGA). Almost all the centers had participated in a clinical evaluation of everolimus for TSC epilepsy and SEGAs in older children, “so there was familiarity and a comfort level” for those indications, Dr. Krueger said.

Everolimus was used much more often than was sirolimus, which probably reflects ongoing clinical development of the drug. A handful of children switched between the two, probably because of side effects. Most centers reported a favorable response. The average initial daily dose of everolimus was 1.05 mg/m²; the average initial daily dose of sirolimus was 0.42 mg/m².

Guidance coming for mTOR inhibitors in infantile TSC

Pages

Recommended Reading