Cost-Effectiveness and Clinical Impact of Antiviral Strategies of HBeAG-Positive and Negative Chronic Hepatitis B

ABSTRACT Introduction. Chronic hepatitis B (CHB) is associated with high burden and healthcare costs. Virologic response achieved with antivirals is associated with progression avoidance. This study aimed to estimate the efficiency and clinical impact of antiviral strategies in CHB patients. Material and methods. A Markov model estimated lifetime complications and direct costs in both, HBeAg-positive and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2 (100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir or entecavir, were compared to no treatment. Progression was based on HBV-DNA levels. Rescue therapy with oral antivirals was applied for peg-IFN failure. Disease costs (€, 2014) and utilities were obtained from literature. Results. Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive, 2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg-positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128 and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost increased up to €102,841 (strategy 1) and €105,408 (strategy 2) in HBeAg-positive, and €85,858 and €93,754 in HBeAg-negative. A€1,581/QALY gained ratio was estimated versus the natural history for both strategies. In conclusion, increasing antiviral coverage would be efficient, reducing complications.

Cost-Effectiveness and Clinical Impact of Antiviral Strategies of HBeAg-Positive and -Negative Chronic Hepatitis B.

INTRODUCTION: Chronic hepatitis B (CHB) is associated with high burden and healthcare costs. Virologic response achieved with antivirals is associated with progression avoidance. This study aimed to estimate the efficiency and clinical impact of antiviral strategies in CHB patients. MATERIAL AND METHODS: A Markov model estimated lifetime complications and direct costs in both, HBeAg-positive and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2 (100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir or entecavir, were compared to no treatment. Progression was based on HBV-DNA levels. Rescue therapy with oral antivirals was applied for peg-IFN failure. Disease costs (C, 2014) and utilities were obtained from literature. RESULTS: Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive, 2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg-positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128 and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost increased up to C102,841 (strategy 1) and C105,408 (strategy 2) in HBeAg-positive, and C85,858 and C93,754 in HBeAg-negative. A C1,581/QALY gained ratio was estimated versus the natural history for both strategies. In conclusion, increasing antiviral coverage would be efficient, reducing complications.

Modeling the cost-effectiveness of different oral antiviral therapies in patients with chronic hepatitis B.

BACKGROUND/AIMS: Chronic hepatitis B (CHB) is a common disease associated with high morbidity, mortality and impact on healthcare costs. Several oral antiviral therapies can lead to complete virologic response, which is associated with prevention of disease progression. The aim of this study was to estimate the cost-effectiveness of the oral antiviral treatments lamivudine, adefovir, telbivudine, entecavir and tenofovir, in patients with CHB. METHODS: A Markov model was used to project the lifetime complications and costs in cohorts of both HBeAg-positive and HBeAg-negative CHB patients treated with one of the above drugs or no treatment. Rescue therapy with two different combination therapies (adefovir plus lamivudine or tenofovir plus entecavir) with their corresponding costs and efficacy rates was also considered. The probabilities of disease progression were based on serum HBV DNA levels. Disease and complication costs were assessed using the perspective of the Spanish National Health System. RESULTS: The highest rate of virologic response was obtained with tenofovir, and this translated to its higher life years saved (LYS) and quality adjusted life years (QALY) compared with the rest of the alternatives in HBeAg-positive and HBeAg-negative patients. Tenofovir is associated with lower costs and higher efficacy over entecavir, telbivudine and adefovir in HBeAg-positive patients, and telbivudine and entecavir in HBeAg-negative patients. The incremental cost-effectiveness ratios with respect to the rest of the alternatives are below the common reference efficiency threshold of 30,000 euro per LYS/QALY. CONCLUSION: In chronic HBV infected patients, tenofovir is a cost-effective or even cost-saving strategy compared with other available treatment options for CHB.

[Adefovir dipivoxil compassionate use program in Spain: efficacy and resistance analysis]. / Programa de uso compasivo con adefovir dipivoxil en España: valoración de su eficacia y estudio de las resistencias.

BACKGROUND AND OBJECTIVE: The extended treatment with lamivudine in patients with chronic hepatitis B is associated with the emergence of resistances. Patients with resistance to lamivudine show a loss of biochemical and virological responses and a higher progression of their liver disease. Adefovir dipivoxil, an analogue of the nucleotides, is effective for the treatment of patients with resistance to lamivudine. The aim of this study was to evaluate the efficacy, safety and resistance of adefovir dipivoxil in patients with chronic hepatitis B refractory to treatment with lamivudine. PATIENTS AND METHOD: One hundred and twenty hepatits B virus patients refractory to lamivudine were treated with adefovir dipivoxil. Seventy-four patients were followed up during two years. In all cases, the hepatitis B virus-DNA was determined by polymerase chain reaction, and in those cases without response to treatment, the presence of resistances to adefovir and lavimudine were studied. RESULTS: At the second year of treatment, we observed a biological response of 54.1%, a biochemical response of 62.2%, while an elimination of hepatitis B e antigen was seen in 21% cases. 20% patients developed resistance to adefovir dipivoxil, and the most frequent detected mutations were: A181V, A181T and N236T. Drug safety was excellent; in fact, only one adverse effect related to the drug was detected. CONCLUSIONS: Treatment with adefovir dipivoxil for 2 years in mono-therapy in patient who are previously non-responders to lavimudine is associated with a high biochemical and virologycal response with an excellent safety. At the second year of treatment, the adefovir dipivoxil resistance rate is 20%.