Mucocutaneous Adverse Events Associated With Oral Sirolimus for the Treatment of Vascular Anomalies

Grenier, Pierre; McCormack, Lindsay; Alshamekh, Shomoukh A.; Adams, Denise M.; Trenor, Cameron C.; O'Hare, Meghan; Liang, Marilyn G.

doi:10.1001/jamadermatol.2020.5180

Cited by 4 publications

(2 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the largest trial published, 78.5% of the AEs were mild to moderate, with mucositis being the most frequent (37.3%), and pneumonitis and respiratory infection being the most severe (18) . In a retrospective review, 55% of the patients had mucocutaneous AEs (20) . In our population, oral sirolimus was well tolerated, and dyslipidemia was the most frequent AE (2 out of 7 patients).…”

Section: Discussionmentioning

confidence: 99%

Treatment with oral or topial sirolimus in complex vascular anomalies in pediatrícs. Experience in a third-level hospital

Oliveira¹,

Roca²,

Tellado³

et al. 2023

Cir Pediatr

View full text Add to dashboard Cite

Objective. The use of sirolimus in vascular anomalies is a special indication not authorized in its data sheet. The objective of this study was to increase the evidence of oral or topical use of sirolimus for this indication in the pediatric population.Materials and methods. An observational, retrospective study of patients under 18 years of age treated with oral or topical sirolimus for vascular anomalies was carried out. Diagnosis and location of lesions, administration route and dosage of sirolimus, blood levels of sirolimus in patients who received oral treatment, treatment duration, response, and toxicity were collected.Results. 18 patients -7 with oral treatment and 11 with topical treatment -were included. With oral sirolimus, the overall response rate was 85.7%. Sirolimus was discontinued in 2 cases -as a result of full resolution and progression. 57.1% of patients had adverse effects, most of which were mild. Dyslipidemia was the most frequent adverse effect. Blood levels were monitored in all patients for dose adjustment purposes. With topical treatment, the overall response rate was 72.7%. Sirolimus was discontinued in 3 cases -due to progression in 2 cases and to stability in 1. 27.3% of patients had adverse effects, with itching standing out as the most frequent one.Conclusions. The favorable results of sirolimus treatment in our patients seem to confirm its effectiveness and safety in vascular anomalies, which make it stand as a therapeutic option in pediatric patients. However, further research is required to establish the optimal treatment regimen, treatment duration, and potential long-term adverse effects.

show abstract

Section: Discussionmentioning

confidence: 99%

Treatment with oral or topial sirolimus in complex vascular anomalies in pediatrícs. Experience in a third-level hospital

Oliveira¹,

Roca²,

Tellado³

et al. 2023

Cir Pediatr

View full text Add to dashboard Cite

show abstract

“…En el mayor ensayo publicado, el 78,5% de los EA fueron leves o moderados; siendo el más frecuente la mucositis (37,3%) y los más graves: neumonitis e infección respiratoria (18) . EA mucocutáneos alcanzaron el 55% de los pacientes en una revisión retrospectiva (20) . En nuestra población, sirolimus oral fue bien tolerado y la dislipemia fue el EA más frecuente (2/7 pacientes).…”

Section: Discussionunclassified

Tratamiento con sirolimus oral o tópico en anomalías vasculares complejas en pediatría. Experiencia en un hospital terciario

Oliveira¹,

Roca²,

Tellado³

et al. 2023

Cir Pediatr

View full text Add to dashboard Cite

C. Fernández Oliveira et al.CIRUGÍA PEDIÁTRICA ResumenObjetivo. El uso de sirolimus en anomalías vasculares es una indicación especial no autorizada en ficha técnica. El objetivo de este estudio es incrementar la evidencia del empleo por vía oral o tópica de sirolimus en esta indicación en población pediátrica.Método. Estudio observacional retrospectivo de pacientes menores de 18 años tratados con sirolimus oral o tópico para anomalías vasculares recogiendo: diagnóstico y ubicación de lesiones, forma de administración y dosificación de sirolimus, niveles sanguíneos de fármaco en los pacientes con tratamiento oral, duración del tratamiento, respuesta y toxicidad.Resultados. Se incluyeron 18 pacientes (7 con tratamiento oral y 11 tópico). Con sirolimus oral, la tasa de respuesta global fue 85,7%. Se interrumpió sirolimus en 2 casos: por resolución completa y por progresión. El 57,1% experimentó algún efecto adverso, en su mayoría leves; siendo la dislipemia el efecto adverso más frecuente. La monitorización de niveles sanguíneos fue empleada en todos los pacientes para el ajuste de dosis. Con el tratamiento tópico, la tasa de respuesta global fue 72,7%. Se interrumpió sirolimus en 3 casos: progresión en 2 casos y estabilidad en 1. El 27,3% experimentó algún efecto adverso, siendo el prurito el más frecuente.Conclusiones. Los resultados favorables del tratamiento con sirolimus en nuestros pacientes parecen confirmar la efectividad y seguridad del fármaco en anomalías vasculares y lo posicionan como una opción terapéutica en pacientes pediátricos. Aun así, parece necesaria mayor investigación que trate de aclarar, entre otros, el régimen óptimo del tratamiento, la duración del mismo y los potenciales efectos adversos a largo plazo.

show abstract

Epilepsy in the mTORopathies: opportunities for precision medicine

Moloney

Cavalleri

Delanty

2021

Brain Communications

View full text Add to dashboard Cite

The mechanistic target of rapamycin (mTOR) signalling pathway serves as a ubiquitous regulator of cell metabolism, growth, proliferation and survival. The main cellular activity of the mTOR cascade funnels through mTOR complex 1, which is inhibited by rapamycin, a macrolide compound produced by the bacterium Streptomyces hygroscopicus. Pathogenic variants in genes encoding upstream regulators of mTOR complex 1 cause epilepsies and neurodevelopmental disorders. Tuberous sclerosis complex is a multisystem disorder caused by mutations in mTOR regulators TSC1 or TSC2, with prominent neurological manifestations including epilepsy, focal cortical dysplasia and neuropsychiatric disorders. Focal cortical dysplasia type II results from somatic brain mutations in mTOR pathway activators MTOR, AKT3, PIK3CA and RHEB and is a major cause of drug-resistant epilepsy. DEPDC5, NPRL2 and NPRL3 code for subunits of the GTPase-activating protein (GAP) activity towards Rags 1 complex (GATOR1), the principal amino acid-sensing regulator of mTOR complex 1. Germline pathogenic variants in GATOR1 genes cause non-lesional focal epilepsies and epilepsies associated with malformations of cortical development. Collectively the mTORopathies are characterised by excessive mTOR pathway activation and drug-resistant epilepsy. In the first large-scale precision medicine trial in a genetically-mediated epilepsy, everolimus (a synthetic analogue of rapamycin) was effective at reducing seizure frequency in people with tuberous sclerosis complex. Rapamycin reduced seizures in rodent models of DEPDC5-related epilepsy and focal cortical dysplasia type II. This review outlines a personalised medicine approach to the management of epilepsies in the mTORopathies. We advocate for early diagnostic sequencing of mTOR pathway genes in drug-resistant epilepsy, as identification of a pathogenic variant may point to an occult dysplasia in apparently non-lesional epilepsy or may uncover important prognostic information including, an increased risk of sudden unexpected death in epilepsy in the GATORopathies or favourable epilepsy surgery outcomes in focal cortical dysplasia type II due to somatic brain mutations. Lastly, we discuss the potential therapeutic application of mTOR inhibitors for drug-resistant seizures in GATOR1-related epilepsies and focal cortical dysplasia type II.

show abstract

Mucocutaneous Adverse Events Associated With Oral Sirolimus for the Treatment of Vascular Anomalies

Cited by 4 publications

References 6 publications

Treatment with oral or topial sirolimus in complex vascular anomalies in pediatrícs. Experience in a third-level hospital

Treatment with oral or topial sirolimus in complex vascular anomalies in pediatrícs. Experience in a third-level hospital

Tratamiento con sirolimus oral o tópico en anomalías vasculares complejas en pediatría. Experiencia en un hospital terciario

Epilepsy in the mTORopathies: opportunities for precision medicine

Contact Info

Product

Resources

About