Eventos adversos do tratamento medicamentoso de pacientes com doenças reumáticas autoimunes na infância: uma coorte retrospectiva em centro único
Data
2018-03-08
Autores
Said, Manar 
Orientadores
Terreri, Maria Teresa De Sande E Lemos Ramos Ascensao
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: As doenças reumáticas autoimunes (DRAIs) são doenças inflamatórias decorrentes de alterações no sistema imunológico, e se manifestam com comprometimento de articulações e de outros órgãos e sistemas. O tratamento inclui anti-inflamatórios, imunossupressores e agentes biológicos. Estas medicações levam ao controle das DRAIs, entretanto podem ocasionar diversos eventos adversos (EAs) de leves a graves, com necessidade de novos medicamentos, redução de dose ou até a suspensão da medicação causadora do EA. Os EAs contribuem para a morbidade da doença ou até mortalidade em alguns casos. A gravidade dos EAs depende da sua dose, via de administração, tempo de utilização e associação medicamentosa, além da presença de outros fatores agravantes. Objetivos: Descrever os EAs dos medicamentos utilizados no tratamento das DRAIs e avaliar sua gravidade, fatores associados, condutas tomadas e evolução destes eventos em pacientes pediátricos com artrite idiopática juvenil (AIJ), lúpus eritematoso sistêmico juvenil (LESJ) e dermatomiosite juvenil (DMJ). Métodos: Trata-se de estudo retrospectivo descritivo e analítico de uma coorte de crianças e adolescentes tratados em centro especializado terciário em reumatologia pediátrica. A pesquisa avaliou todos os EAs dos medicamentos relatados nos prontuários dos pacientes e compilados por meio de questionário específico de cada uma das três doenças e em seguida armazenados em planilhas de excel. Foram avaliadas as associações entre os fatores agravantes ao EA, tais como idade do paciente, dose, via de administração e tempo de uso da medicação, em pacientes tratados com metotrexate e glicocorticóides. Resultados: Dos 662 pacientes (391 com AIJ,162 LESJ e 69 DMJ) de nosso centro, 547 pacientes foram incluídos e 951 EAs foram observados. O MTX foi a medicação mais causadora de EAs que ocorreram em 63,3% dos pacientes, seguida dos glicocorticóides. Outras medicações como ciclofosfamida, ciclosporina, azatioprina, micofenolato, leflunomide, cloroquina, etanercepte, infliximabe, adalimumabe, tocilizumabe, rituximabe e gamaglobulina também causaram EAs. O abatacepte não causou nenhum EA. A maioria dos pacientes com EAs ao MTX apresentou intolerância gastrointestinal e aumento de enzimas hepáticas. Quando estratificados por doença, os EAs foram associados a doses do MTX ≥ 0,6 mg\kg\semana. Doses ≥ 0,5 mg/kg/dia de glicocorticóide foram associadas a aumento de EAs. Por outro lado, o tratamento com pulsoterapia não induziu à ocorrência de EAs. Dois pacientes (0,2%) apresentaram EAs ameaçantes à vida e 35 (3,7%) apresentaram EAs graves. Nenhum caso de morte relacionado à medicação foi registrado. A conduta mais usada frente aos EAs foi a suspensão, redução ou mudança de via de administração da medicação, ou uso de outros medicamentos, além de orientações. Conclusão: Este estudo é unico por ser o maior estudo retrospectivo na literatura a abordar os EAs dos medicamentos utilizados ao longo do tratamento das DRAIs na infância num centro especializado. Foi concluído que os EAs associados ao tratamento das DRAIs são frequentes e necessitam de atenção farmacêutica e avaliação de fatores associados à sua ocorrência tais como idade, dose, tempo, via de administração e doença. Este estudo mostrou que a ocorrência dos EAs pode estar associada à doença avaliada ou a outros medicamentos combinados.
Introduction: Autoimmune rheumatic diseases (AIRDs) are inflammatory diseases caused by changes in the immune system, and are manifested by joint involvement, as well as involvement of other organs and systems. Treatment includes anti-inflammatories, immunosuppressants and biological agents. These medications lead to the control of AIRDs, however they can result in several adverse events (AE) that vary in severity, requiring the use of other medications, dose reduction or even the suspension of the medication that caused the AE. AEs contribute to disease morbidity or even mortality in some cases. The severity of AEs depends on its dose, route of administration, duration of use, drug association, or presence of other risk factors.Objectives: To describe the AEs of the drugs used to treat AIRDs and to assess their severity, associated factors, medical conduct taken and evolution of these events in pediatric patients with juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM).Methods: retrospective descriptive and analytical study of a cohort of children and adolescents treated at a tertiary center specialized in pediatric rheumatology. The study evaluated all the AEs of the drugs reported in the patient's charts. The data were compiled through a specific questionnaire for each disease and then stored in excel spreadsheets.The associations between the aggravating factors for the AEs, such as patient age, dose, route of administration, and time of use of the medication, were evaluated in patients treated with methotrexate (MTX) and glucocorticoids. Results: From 662 patients (391 JIA,162 JSLE e 69 JDM) of our center, 547 patients were included and 951 AEs were recorded. MTX was the most common cause of AEs occurring in 63.3% of patients, followed by glucocorticoids. Other medications such as cyclophosphamide, cyclosporine, azathioprine, mycophenolate, leflunomide, chloroquine, etanercept, infliximab, adalimumab, tocilizumab, rituximab and human immunoglobulin also caused AEs. Abatacept did not cause any EA. Most patients with MTX-associated AEs had gastrointestinal intolerance and increased liver enzyme levels. When the AEs were estratificated by disease, they were associated to MTX doses ≥ 0.6 mg / kg / week. Doses ≥ 0.5 mg/kg/day of glucocorticoids were associated with increased AEs. On the other hand, treatment with pulsetherapy with corticosteroid did not induce to AEs. Two patients (0.2%) had life-threatening AEs and 35 (3.7%) had severe AEs. No death related to medication was recorded. The medical conducts most taken against the AEs were suspension, reduction or change in route of administration, or use of other medications, besides orientations to the patients. Conclusion: This study is original because it is the largest retrospective study in the literature that focused on the AEs of all medications used during the treatment of AIRDs throughout childhood in a specialized center. I was concIuded that the AEs associated with the treatment of AIRDs are frequent and require pharmaceutical care and the associated factors to the occurrence of AEs such as age, dose, time of treatment, route of administration should be evaluated. This study showed that the occurrence of AE may be related to the disease itself or other associated treatments.
Introduction: Autoimmune rheumatic diseases (AIRDs) are inflammatory diseases caused by changes in the immune system, and are manifested by joint involvement, as well as involvement of other organs and systems. Treatment includes anti-inflammatories, immunosuppressants and biological agents. These medications lead to the control of AIRDs, however they can result in several adverse events (AE) that vary in severity, requiring the use of other medications, dose reduction or even the suspension of the medication that caused the AE. AEs contribute to disease morbidity or even mortality in some cases. The severity of AEs depends on its dose, route of administration, duration of use, drug association, or presence of other risk factors.Objectives: To describe the AEs of the drugs used to treat AIRDs and to assess their severity, associated factors, medical conduct taken and evolution of these events in pediatric patients with juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM).Methods: retrospective descriptive and analytical study of a cohort of children and adolescents treated at a tertiary center specialized in pediatric rheumatology. The study evaluated all the AEs of the drugs reported in the patient's charts. The data were compiled through a specific questionnaire for each disease and then stored in excel spreadsheets.The associations between the aggravating factors for the AEs, such as patient age, dose, route of administration, and time of use of the medication, were evaluated in patients treated with methotrexate (MTX) and glucocorticoids. Results: From 662 patients (391 JIA,162 JSLE e 69 JDM) of our center, 547 patients were included and 951 AEs were recorded. MTX was the most common cause of AEs occurring in 63.3% of patients, followed by glucocorticoids. Other medications such as cyclophosphamide, cyclosporine, azathioprine, mycophenolate, leflunomide, chloroquine, etanercept, infliximab, adalimumab, tocilizumab, rituximab and human immunoglobulin also caused AEs. Abatacept did not cause any EA. Most patients with MTX-associated AEs had gastrointestinal intolerance and increased liver enzyme levels. When the AEs were estratificated by disease, they were associated to MTX doses ≥ 0.6 mg / kg / week. Doses ≥ 0.5 mg/kg/day of glucocorticoids were associated with increased AEs. On the other hand, treatment with pulsetherapy with corticosteroid did not induce to AEs. Two patients (0.2%) had life-threatening AEs and 35 (3.7%) had severe AEs. No death related to medication was recorded. The medical conducts most taken against the AEs were suspension, reduction or change in route of administration, or use of other medications, besides orientations to the patients. Conclusion: This study is original because it is the largest retrospective study in the literature that focused on the AEs of all medications used during the treatment of AIRDs throughout childhood in a specialized center. I was concIuded that the AEs associated with the treatment of AIRDs are frequent and require pharmaceutical care and the associated factors to the occurrence of AEs such as age, dose, time of treatment, route of administration should be evaluated. This study showed that the occurrence of AE may be related to the disease itself or other associated treatments.
Descrição
Citação
SAID, Manar Amanouil. Eventos adversos do tratamento medicamentoso de pacientes com doenças reumáticas autoimunes na infância: uma coorte retrospectiva em um centro único. 2018. 118 f. Dissertação (Mestrado em Pediatria) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2018.