Sirolimus: Long-term safety and influence on growth in patients
Sirolimus and everolimus (Afinitor) are both mTOR inhibitors. They block a protein called mTOR complex 1 that helps control how cells grow, divide, and survive. By blocking mTOR, these drugs slow down processes that can cause uncontrolled growth, such as in tumours or abnormal tissue. While sirolimus and everolimus show similar effectiveness in clinical trials, in Australia, everolimus is the most commonly used mTOR inhibitor in TSC. Sirolimus is used in topical creams to treat facial angiofibromas. You can find more information about mTOR inhibitor treatments for TSC here.
About this study
This study looked at the long-term safety of sirolimus, focusing on its effects on growth in children. Sirolimus is often used to treat conditions such as TSC and LAM which are linked to the overactivation of the mTOR pathway. Despite the usefulness of sirolimus in managing these conditions, there is limited research on its long-term safety, especially in children.
How the study was conducted
Researchers analysed data from two long-term studies involving 1,738 people aged 5 days to 69 years. Participants who had never previously received sirolimus were given the drug at carefully adjusted doses for up to 10 years. Researchers monitored participants’ growth (height, weight, and BMI), as well as their blood, liver and kidney function, and cholesterol levels. They also recorded any side effects experienced during the treatment.
Outcomes of the study
Based on the data collected, the researchers found that sirolimus did not disrupt normal growth in children, although higher doses were linked to slight increases in height, weight, and BMI. Temporary increases in red and white blood cell counts and cholesterol levels, were noted, especially in the first year of treatment. Other measures, like liver and kidney function, stayed stable. Common side effects included mouth sores, stomach issues (nausea, diarrhoea) and menstrual irregularities in women. Most of these were mild and resolved with dose adjustments. Rare serious side effects were observed, but they were not common enough to suggest widespread concern.
Conclusions of the study
The researchers conclude that sirolimus appears safe for long-term use in managing TSC and LAM. While it is generally well-tolerated, some side effects require monitoring. The potential link between higher doses and slightly increased growth measures needs further research.
Implications of the study
This study supports the long-term safety of sirolimus in children and adults with TSC and/or LAM. It also provides valuable insights into managing side effects and adjusting doses to maximise safety.
Wang YY, Zou LP, Xu KF, Xu WS, Zhang MN, Lu Q, Tian XL, Pang LY, He W, Wang QH, Gao Y, Liu LY, Chen XQ, Ma SF, Chen HM, Dun S, Yang XY, Luo XM, Huang LL, Li YF. Long-term safety and influence on growth in patients receiving sirolimus: a pooled analysis. Orphanet J Rare Dis. 2024 Aug 15;19(1):299. doi: 10.1186/s13023-024-03243-5. PMID: 39148107; PMCID: PMC11325711.
Full paper available at: https://doi.org/10.1186/s13023-024-03243-5
DISCLAIMER
This information is intended to provide some insights into recent TSC-related research. It is not intended to, and it should not, constitute medical or other advice. Readers are warned not to take any action without first seeking medical advice.