Publication: El uso de fármacos antrirretrovirales no aprobados en niños en la cohorte pediátrica con infección VIH de la Comunidad de Madrid
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2015-02-10
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Universidad Complutense de Madrid
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Abstract
La infección por el VIH en niños tiene una progresión más rápida que en adultos y el arsenal terapéutico disponible es escaso, haciendo que haya que tratar fuera de las indicaciones de la ficha técnica (off-label) Estudiamos uso de fármacos off-label en la Cohorte de niños menores de 18 años, infectados por el VIH en la Comunidad de Madrid. Estudio retrospectivo de cohortes multicéntrico de Marzo 1988-Diciembre 2011. Se excluyeron pacientes fallecidos y aquellos infectados por vía no vertical. Comparamos los pacientes tratados off-label con los tratados acorde a ficha técnica, encontramos significativo; menor edad al diagnóstico (1.7 vs 3.5 años), etnia blanco-caucasiana (79% vs 67%), nacidos en España (89% vs 75%), tasa de coinfección por el virus de la hepatitis C (8.6% vs 1.1%), peor situación clínica según la clasificación CDC (estadio C 35% vs 13%) y menor media del porcentaje de los CD4 nadir (14 vs 17%). Un 70% de los pacientes recibió fármacos off-label, un 23% de todas las prescripciones. Los motivos de prescripción off-label fueron inicio o fallo de tratamiento, durante los primeros años de la epidemia, tras 2001 también para simplificar el mismo. Los efectos secundarios tras uso off-label fueron frecuentes (34%), de predominio gastrointestinal (52%). Llevaron a la suspensión en el 12% de los casos. Un 10% de los niños tratados off-label fueron sobredosificados y un 10% infradosificados. Se encontró fallo en el tratamiento en el 50% de los infradosificados vs, 26% en los que recibieron la dosis correcta (p<0.05). Problemas con la ingesta del fármaco llevó a su suspensión en un 3%, generalmente cuando la formulación no era apropiada para la edad (p<0.05). Se necesita disponer de más datos de farmacocinética para evitar el riesgo de sobredosificación e infradosificación y evitar exponer a los niños a selección de resistencias y fallo de tratamiento.
HIV infected children have a different immune response and evolution of the disease when compared to adults. There are few therapeutic options, especially in the very young, where off-label use or ARV is common. We determined the off-label use in the cohort of children and adolescents under 18 years living with HIV in Madrid. We designed a retrospective multicenter cohort study from March 1988 to December 2011. We excluded patients who died and those of non vertical transmission. When comparing the patients treated off-label with those that received approved for age and weight drugs, we found significant; lower age at diagnosis (1.7 vs 3.5 years), white Caucasian ethnicity (79% vs 67%), to be born in Spain (89% vs 75%), higher rate of hepatitis C confection (8.6 % vs 1.1 % ), worse clinical status according to the CDC classification (stage C 35 % vs 13 %) and lower mean percentage of CD4 nadir (14% vs 17%). We found that 70% of the patients took off-label drugs, 23% of all the prescriptions. The main reasons for prescribing off-label were for starting treatment and after treatment failure, during the first years of the epidemic, and after 2001 also treatment simplification. Side effects after off-label use was common (34%), mainly mild gastrointestinal symptoms (52%), and this led to treatment interruption in 12% of the cases. Up to 10% of ARV were overdosed and 10% underdosed (25% above or below the recommended dose). Treatment failure occurred in 50% of underdosed vs, 26% non-underdosed (p< 0.05). Problems taking the drug led to withdrawal in 3%, more likely when formulation was not suitable for age (p<0.05). Pharmacokinetic studies are needed as misdosing may occur when prescribing off-label. Most importantly, underdosing may lead to treatment failure due to resistance.
HIV infected children have a different immune response and evolution of the disease when compared to adults. There are few therapeutic options, especially in the very young, where off-label use or ARV is common. We determined the off-label use in the cohort of children and adolescents under 18 years living with HIV in Madrid. We designed a retrospective multicenter cohort study from March 1988 to December 2011. We excluded patients who died and those of non vertical transmission. When comparing the patients treated off-label with those that received approved for age and weight drugs, we found significant; lower age at diagnosis (1.7 vs 3.5 years), white Caucasian ethnicity (79% vs 67%), to be born in Spain (89% vs 75%), higher rate of hepatitis C confection (8.6 % vs 1.1 % ), worse clinical status according to the CDC classification (stage C 35 % vs 13 %) and lower mean percentage of CD4 nadir (14% vs 17%). We found that 70% of the patients took off-label drugs, 23% of all the prescriptions. The main reasons for prescribing off-label were for starting treatment and after treatment failure, during the first years of the epidemic, and after 2001 also treatment simplification. Side effects after off-label use was common (34%), mainly mild gastrointestinal symptoms (52%), and this led to treatment interruption in 12% of the cases. Up to 10% of ARV were overdosed and 10% underdosed (25% above or below the recommended dose). Treatment failure occurred in 50% of underdosed vs, 26% non-underdosed (p< 0.05). Problems taking the drug led to withdrawal in 3%, more likely when formulation was not suitable for age (p<0.05). Pharmacokinetic studies are needed as misdosing may occur when prescribing off-label. Most importantly, underdosing may lead to treatment failure due to resistance.
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Pediatría, leída el 14-03-2014