Avaliação da eficácia do ivacaftor: análise crítica dos desfechos utilizados
Avaliação da eficácia do ivacaftor: análise crítica dos desfechos utilizados
Arquivos
Data
2016
Autores
Souza, Charlles Zapp de
Journal Title
Journal ISSN
Volume Title
Publisher
Instituto Nacional de Cardiologia
Resumo
A fibrose cística é uma doença rara cuja incidência está relacionada com as etnias,
sendo mais frequente em caucasianos. A doença pulmonar impacta negativamente
na sobrevida destes pacientes e muitos morrem no final da adolescência ou início
dos 20 anos em decorrência das infecções respiratórias recorrentes. Atualmente
encontram-se disponíveis diversas opções terapêuticas para o cuidado desta
doença, porém são direcionados para redução dos sintomas e complicações
decorrentes desta; não há cura para a fibrose cística. Assim, as novas terapias
direcionadas ao problema subjacente da doença ganharam destaque. Ivacaftor
representa a primeira droga moduladora da proteína CFTR, e esta dissertação teve
como objetivos realizar uma revisão rápida sobre a eficácia e segurança deste
medicamento em pacientes com fibrose cística portadores da mutação G551D e
identificar e analisar criticamente os desfechos utilizados para medir esta eficácia. A
partir de uma busca sistemática em seis bases distintas, foram identificadas duas
revisões sistemáticas; uma incluiu quatro ECR totalizando 392 pacientes e a outra
dois ECR e um estudo de extensão totalizando 213 pacientes. Os estudos
identificados pelas revisões sistemáticas utilizaram como resultado, sobretudo, um
desfecho substituto denominado volume expiratório forçado no primeiro segundo,
para o qual se observou uma forte magnitude de efeito com a utilização deste
medicamento, e o aumento em VEF1. A relação do VEF1 com qualidade de vida nos
estudos envolvendo ivacaftor foram observadas por meio de um questionário
específico da doença (Cystic Fibrosis Questionnaire-Revised). Dados sobre
mortalidade não foram relatados em nenhum estudo, embora a correlação entre
VEF1 e mortalidade seja sugerida pelos estudos observacionais identificados na
literatura. Observou-se também que não houve a realização de novos estudos sobre
ivacaftor desde sua regulamentação nos mercados americano e europeu e sim a
compilação dos já existentes. Desta forma, conclui-se que a intervenção é eficaz
quando se considera desfechos substitutos como o VEF1, sendo necessários mais
estudos para comprovação de forma inequívoca de sua relação com desfechos
realmente relevantes aos pacientes.
Cystic fibrosis is a rare disease whose incidence is related to ethnicity, being more frequent in caucasians. Pulmonary disease has a negative impact on the survival of these patients and many of them die in late adolescence or early 20 years as a result of recurrent respiratory infections. Several therapeutic options are currently available for the care of this disease, but they are directed to reduce the symptoms and complications arising from it; there is no cure for cystic fibrosis. Thus, the new therapies directed to the underlying problem of the disease gained prominence. Ivacaftor represents the first CFTR modulatory drug, and this dissertation aimed to conduct a rapid review of the efficacy and safety of this drug in cystic fibrosis patients with the G551D mutation and to identify and critically analyze the outcomes used to measure this efficacy. From a systematic search on six distinct bases, two systematic reviews were identified; one review included four randomized clinical trials totalizing 392 patients and the other included two randomized clinical trials and one extension study totalizing 213 patients. The studies identified by the systematic reviews mainly used a surrogate outcome called forced expiratory volume in the first second, for which a strong magnitude of effect was observed with the use of this drug, in FEV1 gain. The relationship of FEV1 with quality of life in studies involving ivacaftor were observed through a disease-specific questionnaire (Cystic Fibrosis Questionnaire- Revised). Mortality data were not reported in the studies, although through the identification of observational studies the correlation between FEV1 and mortality is suggested. It was also observed that there were no new studies on ivacaftor since its regulation in the American and European markets, but the compilation of the existing ones. Thus, it is concluded that the intervention is effective when considering surrogate outcomes such as FEV1, and more studies are needed to unequivocally prove their relationship with outcomes that are truly relevant to patients.
Cystic fibrosis is a rare disease whose incidence is related to ethnicity, being more frequent in caucasians. Pulmonary disease has a negative impact on the survival of these patients and many of them die in late adolescence or early 20 years as a result of recurrent respiratory infections. Several therapeutic options are currently available for the care of this disease, but they are directed to reduce the symptoms and complications arising from it; there is no cure for cystic fibrosis. Thus, the new therapies directed to the underlying problem of the disease gained prominence. Ivacaftor represents the first CFTR modulatory drug, and this dissertation aimed to conduct a rapid review of the efficacy and safety of this drug in cystic fibrosis patients with the G551D mutation and to identify and critically analyze the outcomes used to measure this efficacy. From a systematic search on six distinct bases, two systematic reviews were identified; one review included four randomized clinical trials totalizing 392 patients and the other included two randomized clinical trials and one extension study totalizing 213 patients. The studies identified by the systematic reviews mainly used a surrogate outcome called forced expiratory volume in the first second, for which a strong magnitude of effect was observed with the use of this drug, in FEV1 gain. The relationship of FEV1 with quality of life in studies involving ivacaftor were observed through a disease-specific questionnaire (Cystic Fibrosis Questionnaire- Revised). Mortality data were not reported in the studies, although through the identification of observational studies the correlation between FEV1 and mortality is suggested. It was also observed that there were no new studies on ivacaftor since its regulation in the American and European markets, but the compilation of the existing ones. Thus, it is concluded that the intervention is effective when considering surrogate outcomes such as FEV1, and more studies are needed to unequivocally prove their relationship with outcomes that are truly relevant to patients.
Description
Palavras-chave
Ivacaftor, Qualidade de vida, Mortalidade, Exacerbações pulmonares, Volume expiratório forçado no primeiro segundo, Fibrose cística, Ivacaftor, Quality of life, Mortality, Pulmonary exacerbations, Forced expiratory volume in the first second, Cystic fibrosis
Citação
Souza CZ. Avaliação da eficácia do ivacaftor: análise crítica dos desfechos utilizados. Rio de Janeiro. Dissertação [Mestrado Profissional em Avaliação de Tecnologias em Saúde] Instituto Nacional de Cardiologia - INC; 2016.