Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil

Abstract

Introduction: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. Methods: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. Results: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. Conclusions: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

Cost-effectiveness analysis is a mandatory strategy for health systems: evidence from a study involving therapies for hepatitis C

“…Despite the limitations, this work is relevant for analyzing the incorporation of drugs associated with high costs into a public health system. The effectiveness data of this and other phase IV studies indicated that premarketing trials overestimated the effectiveness of TT 19,20,21,34 .…”

Avaliação da efetividade e segurança dos novos fármacos de ação direta indicados no tratamento da hepatite C

“…Verificou-se taxa de RVS média de 56,6% (51,9% para BOC e 58% para TVR) e reações adversas severas ocorreram em 44,2% dos pacientes, com seis mortes registradas(CALLEFI et al, 2017). Em outro estudo multicêntrico brasileiro, realizado por Lobato e colaboradores, encontrou-se taxa global de RVS de 54,2% e observou-se ocorrência de reações adversas em 87,5% dos pacientes(LOBATO et. al., 2018).…”

“…al., 2018). Em estudo realizado no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, com uma amostra de 115 pacientes que receberam terapia tripla, 61,7% alcançaram RVS (58,3% para BOC e 62,1% para TVR) (RODRIGUES, 2017).Além das taxas de RVS insatisfatórias encontradas e da elevada incidência de reações adversas, a terapia com os IPs de primeira geração apresentava um alto custo e esquemas posológicos complicados, onde tanto BOC quanto TVR deveriam ser administrados diversas vezes ao dia e sua absorção no trato gastrointestinal dependia da quantidade de alimentos gordurosos ingeridos concomitantemente, fatores que dificultavam a adesão ao tratamento(LOBATO et. al., 2018).…”