Short-term safety of mTOR inhibitors in infants and very young children with tuberous sclerosis complex (TSC): Multicentre clinical experience.
Por:
Krueger DA, Capal JK, Curatolo P, Devinsky O, Ess K, Tzadok M, Koenig MK, Narayanan V, Ramos F, Jozwiak S, de Vries P, Jansen AC, Wong M, Mowat D, Lawson J, Bruns S, Franz DN and TSCure Research Group
Publicada:
1 nov 2018
Ahead of Print:
4 jul 2018
Resumen:
OBJECTIVE: To evaluate the safety of mTOR inhibitors (sirolimus or everolimus) in infants and very young children with tuberous sclerosis complex (TSC) under two years of age. METHODS: Study design was retrospective to capture medical record data from 52 international TSC Centres who initiated treatment with sirolimus or everolimus in TSC children before the age of two years. Data collection included demographic and clinical information including reason(s) for initiating treatment with mTOR inhibitors, treatment duration, dosing, and corresponding serum trough levels, response to treatment, and adverse events (AE). RESULTS: 19 of 52 (37%) TSC Centres reported treatment of at least one child with TSC under the age of two years with everolimus or sirolimus. Treatment-related data were provided for 45 patients meeting inclusion criteria. Everolimus was utilised 87% of the time, compared to 24% for sirolimus (5 subjects, 11%, were treated separately with both). Refractory epilepsy (45%) was the most common primary reason for initiating treatment and treatment was initiated on average at 11.6 ± 7.6 months of age. At least one AE, suspected or definitely treatment-related, occurred in 35 of 45 (78%) treated subjects. Most AEs were mild (Grade 1) or moderate (Grade 2) in severity and most commonly related to infections. Severe AE (Grade 3) was reported in 7 subjects (20%) and no life-threatening AE (Grade 4) or death/disability (Grade 5) was reported. Treatment was discontinued due to an AE in 9 of 45 (20%). CONCLUSIONS: Everolimus, and to a lesser extent sirolimus, are increasingly being used to treat TSC infants and very young children for multiple TSC-associated clinical indications. While AEs were common, most were not severe and did not prevent continued treatment in the majority of this younger population.
Filiaciones:
Krueger DA:
Department of Neurology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
Capal JK:
Department of Neurology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
Curatolo P:
Child Neurology and Psychiatry Unit, Systems Medicine Department, University Hospital Tor Vergata, Rome, Italy
Devinsky O:
Langone Medical Center, New York University, New York, New York, USA
Ess K:
Monroe Carell Jr Children's Hospital, Vanderbilt University Medical Center, Nashville, TN, USA
Tzadok M:
Pediatric Neurology Unit, Edmond and Lilly Safra Children Hospital, Chaim Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel HaShomer, Tel Aviv, Israel
Koenig MK:
University of Texas at Houston, Houston, TX, USA
Narayanan V:
Arizona Pediatric Neurology and Neurogenetics Associates, Phoenix, AZ, USA
Ramos F:
Department of Neurology, Sant Joan de Deu Hospital, Barcelona, Spain
Jozwiak S:
Department of Pediatric Neurology, Warsaw Medical University, Poland and Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland
de Vries P:
Division of Child Adolescent Psychiatry, University of Cape Town, Cape Town, South Africa
Jansen AC:
Pediatric Neurology Unit, UZ Brussel, Brussels, Belgium
Wong M:
Washington University St. Louis, St. Louis, MO, USA
Mowat D:
Sydney Children's Hospital, Sydney, Australia
Lawson J:
Sydney Children's Hospital, Sydney, Australia
Bruns S:
Department of Neurology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
Franz DN:
Department of Neurology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
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