Adherence and perceived barriers to oral antiviral therapy for chronic hepatitis B.

BACKGROUND: Globally, of the 248 million people chronically infected with the hepatitis B virus (HBV), 74 million reside in China. Five oral nucleot(s)ide analogs (NUCs) have been approved for the treatment of chronic hepatitis B (CHB) in China. OBJECTIVES: The aims of this study were to determine rates of adherence to NUC therapy in patients with CHB, to identify the self-perceived barriers to adherence, and to examine the factors associated with adherence. METHODS: Questionnaire-based interviews were administered among Chinese patients with CHB at hepatology clinics of a tertiary hospital in the city of Wuhan, China. Adults aged 18 years or older prescribed with NUCs were recruited and interviewed to complete a 27-item questionnaire in a private setting, and adherence was measured using the Morisky Medication Adherence Scale (MMAS-8). RESULTS: Among 369 participants, only 16.5% had high adherence (score of 8), 32.2% had medium adherence (score of 6 to <8), and 51.2% were measured with low adherence (score of <6). A logistic regression model was used to determine the factors associated with medication adherence. Significant predictors of high adherence consisted of urban residency, non-cirrhotic status, not using prescribed pills other than HBV medications, and reminders from family members. The five most common reasons for skipping NUCs were that medication(s) are expensive (48.7%), forgetfulness (45.1%), have experienced or worry about potential side effects (19.8%), do not want others to know about my medication(s) usage (18.5%), and ran out of pills and do not have time to refill (15.9%). CONCLUSIONS: This study revealed that adherence rates to oral antiviral therapy were far from optimal. This finding should generate public attention, and it would be beneficial for interventional programs to target Chinese patients from rural regions, as well as patients with low socioeconomic status, cirrhosis, and taking multiple medications.

Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients.

BACKGROUND/AIM: Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). METHODS: To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. RESULTS: In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. CONCLUSION: ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients.

Optimizing HIV treatment.

PURPOSE OF REVIEW: There are at least seven million people eligible for antiretroviral treatment but not receiving it. An additional 19 million people will need to start treatment in the future, as their HIV disease progresses. Funding for Universal Access to HIV treatment has been restricted by the Global Financial Crisis. RECENT FINDINGS: There are three large randomized trials ongoing, designed to establish the efficacy of lower than approved doses of antiretrovirals. If successful, the results of these trials could lower costs of antiretrovirals and improve the safety profiles. Clinical trials evaluating efavirenz, atazanavir, ritonavir and stavudine are discussed. The costs of these and other antiretrovirals are presented. SUMMARY: The results of these trials could significantly lower the costs of Universal Access. Assuming 15 million people on antiretroviral treatment, the reduction in unit costs of tenofovir (TDF)/3TC/efavirenz from dose optimization of efavirenz to 400 mg once daily would save US$16 per person, leading to an overall saving of US$192 million per year. The switch from zidovudine (ZDV)/3TC/atazanavir (ATV)/r 300/100 once daily to dolutegravir along with ATV/r 200/50 once daily would save US$267 per person, leading to an overall saving of US$801 million. The combined saving in costs from first- and second-line treatment would therefore be US$993 million per year.

Cost-effectiveness of telbivudine versus lamivudine for chronic hepatitis B.

BACKGROUND AND AIM: Chronic hepatitis B is a highly prevalent disease worldwide, leading to serious consequences if not properly treated. Six treatment options for chronic hepatitis B are currently provided by the Brazilian public health system. Telbivudine is a nucleoside analogue that is neither included in the Brazilian clinical protocol nor in the therapeutic guidelines for chronic hepatitis B. OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of telbivudine for the viewpoint of the Brazilian public system, comparing it to lamivudine. METHODS: A Markov model was used to project lifetime complications and costs of treatment with lamivudine or telbivudine for chronic hepatitis B in both HBeAg-positive and HBeAg-negative patients. To evaluate disease progression, probabilities and utilities of virologic response, virologic resistance, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, treatment, interruption of treatment, death and seroconversion were collected in systematic reviews. Costs were collected in DATASUS, ABC da Saúde and scientific literature. RESULTS: Higher rate of virologic response and seroconversion was obtained with telbivudine, and also higher values of quality adjusted life years. However lamivudine is associated with lower costs and also lower cost-effectiveness values. The incremental cost-effectiveness ratios for telbivudine, when compared with lamivudine, were US$ 30,575 and US$ 40,457, respectively for HBeAg-positive and HBeAg-negative patients. CONCLUSION: In chronic hepatitis B lamivudine is a more cost-effective or even cost-saving strategy when compared with telbivudine.

Cost-effectiveness of telbivudine versus lamivudine for chronic hepatitis B

BACKGROUND AND AIM: Chronic hepatitis B is a highly prevalent disease worldwide, leading to serious consequences if not properly treated. Six treatment options for chronic hepatitis B are currently provided by the Brazilian public health system. Telbivudine is a nucleoside analogue that is neither included in the Brazilian clinical protocol nor in the therapeutic guidelines for chronic hepatitis B. OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of telbivudine for the viewpoint of the Brazilian public system, comparing it to lamivudine. METHODS: A Markov model was used to project lifetime complications and costs of treatment with lamivudine or telbivudine for chronic hepatitis B in both HBeAg-positive and HBeAg-negative patients. To evaluate disease progression, probabilities and utilities of virologic response, virologic resistance, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, treatment, interruption of treatment, death and seroconversion were collected in systematic reviews. Costs were collected in DATASUS, ABC da Saúde and scientific literature. RESULTS: Higher rate of virologic response and seroconversion was obtained with telbivudine, and also higher values of quality adjusted life years. However lamivudine is associated with lower costs and also lower cost-effectiveness values. The incremental cost-effectiveness ratios for telbivudine, when compared with lamivudine, were US$ 30,575 and US$ 40,457, respectively for HBeAg-positive and HBeAg-negative patients. CONCLUSION: In chronic hepatitis B lamivudine is a more cost-effective or even cost-saving strategy when compared with telbivudine.

Cost-effectiveness of nucleoside analog therapy for hepatitis B in China: a Markov analysis.

OBJECTIVES: The aim of this study was to investigate the economic consequences of nucleoside analog therapy for hepatitis B treatment in China. METHODS: A cost-utility analysis of treatments for HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) was conducted using a Markov model, in which patients' yearly transitions between different health states were tracked. Patients were tracked as they moved between the following health states: CHB, HBeAg seroconversion (HBeAg-positive CHB patients can have this special health state), virologic resistance, virologic response, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and death. The transition parameters were derived either from systematic reviews of the literature or from previous economic studies. Cost and utility data came from studies based on a Chinese CHB cohort. One-way sensitivity analyses as well as second-order Monte Carlo and probabilistic sensitivity analyses were performed. RESULTS: The entecavir strategy yielded the most quality-adjusted life years (QALYs) for both HBeAg-positive and HBeAg-negative patients when compared with the "no treatment," the lamivudine, the adefovir, and the telbivudine strategies. The risks of complications and mortality also decreased. In the economic analysis, the "no treatment" strategy was the least effective, whereas the entecavir strategy was both the least expensive and the most cost-effective option, followed by telbivudine and lamivudine. The probabilistic sensitivity analysis showed that the entecavir strategy would result in improved cost-effectiveness in >90% of cases at a threshold of $20,000 per QALY. In a one-way sensitivity analysis, the most influential parameters impacting the model's robustness were the utilities of the CHB and virologic response health states. CONCLUSIONS: In China, when treating both HBeAg-positive and HBeAg-negative CHB populations, entecavir is the most cost-effective option when compared with lamivudine, adefovir, and telbivudine.

Cost-effectiveness analysis of roadmap models in chronic hepatitis B using tenofovir as the rescue therapy.

BACKGROUND: The roadmap approach is recommended to guide chronic hepatitis B treatment. We evaluated the cost-effectiveness of various treatment strategies in the global market. METHODS: Lamivudine and telbivudine were tested in roadmap models with switch-to tenofovir if HBV was detectable at week 24 or add-on tenofovir if resistance developed at year 1. Tenofovir and entecavir were tested as continuous monotherapy. In the reference arm, lamivudine was used with add-on tenofovir if resistance developed at year 1. The primary measure of effectiveness was undetectable HBV DNA at year 2. Cost-effectiveness was measured by incremental cost-effectiveness ratio (ICER) in US dollars against the reference arm. RESULTS: In the US and Germany, costs of the reference arms were US $14,486 and US $9,998 for hepatitis B e antigen (HBeAg)-positive and US $11,398 and US $7,531 for HBeAg-negative patients, respectively. In HBeAg-positive patients, the lamivudine roadmap was most cost-effective (ICER US $15,260 in the US and US $29,113 in Germany) with comparable effectiveness (75.1%) to other strategies. In HBeAg-negative patients, tenofovir and entecavir monotherapies were most effective (91-96%) and cost-effective (ICER US $31,297-43,387 in the US and US $53,976-59,822 in Germany). In Asia, where telbivudine cost was lower, both telbivudine and lamivudine roadmaps were cost-effective in HBeAg-positive patients. Tenofovir would be most cost-effective in HBeAg-negative patients if its cost equaled that of telbivudine in Asia. CONCLUSIONS: In HBeAg-positive patients, lamivudine roadmap was most cost-effective; in Asia, telbivudine roadmap had comparable cost-effectiveness to lamivudine roadmap because of the relatively low price of telbivudine. In HBeAg-negative patients, entecavir and tenofovir monotherapies were more cost-effective than the roadmap models.

Telbivudine for the treatment of chronic hepatitis B infection.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of telbivudine for the treatment of chronic hepatitis B (CHB) in adults based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from one randomised controlled trial (RCT) (GLOBE) of reasonable methodological quality comparing telbivudine with lamivudine. One other RCT that appeared to meet the inclusion criteria was excluded from the submission. For the primary outcome of therapeutic response telbivudine was statistically superior to lamivudine at weeks 52 and 104 for hepatitis B e antigen (HBeAg)-positive patients, and at week 104 for HBeAg-negative patients. There were statistically significant differences in favour of telbivudine for some secondary outcomes at 2 years including hepatitis B virus (HBV) DNA reduction, HBV DNA non-detectability and alanine aminotransferase normalisation though not for HBeAg-positive patients. In HBeAg-positive patients there was no significant difference between treatment groups for HBeAg loss or seroconversion at any time point. The incidence of adverse events was similar between treatments. Two RCTs comparing entecavir with lamivudine were included in the indirect comparison; however, this was poorly conducted and the results should be treated with caution. The manufacturer developed two economic models to determine the cost-effectiveness of telbivudine. Evidence on the efficacy of telbivudine and lamivudine was taken from the GLOBE trial; efficacy of adefovir was based on assumption. There was a lack of critical assessment and assurance of the quality of the data used to populate the models. The manufacturer concluded that telbivudine is a cost-effective option compared with lamivudine using evidence from the viral load model [HBeAg-positive patients/HBeAg-negative patients: mean incremental cost 19,087 pounds/49,003 pounds, mean quality-adjusted life-year (QALY) gain 1.30/4.67, incremental cost-effectiveness ratio (ICER) 14,665 pounds/10,497 pounds per QALY]. Resubmitted results after a request for clarification by the ERG gave less favourable ICERs (HBeAg-positive patients/HBeAg-negative patients: mean incremental cost 23,983 pounds/41,910 pounds, mean QALY gain 1.56/2.07, ICER 15,377 pounds/20,256 pounds per QALY). The manufacturer concluded that telbivudine is a cost-effective option (on its own or followed by adefovir) for patients who have developed resistance to first-line telbivudine treatment; however, the presentation of the results was not ideal. In conclusion, although telbivudine was statistically superior to lamivudine for most antiviral outcomes, the difference was not clinically significant; in addition, the cost-effectiveness evidence for telbivudine presented in the manufacturer's submission was limited. The NICE guidance issued as a result of the STA states that telbivudine is not recommended for the treatment of chronic hepatitis B and that people currently receiving telbivudine should have the option to continue therapy until they and their clinicians consider it appropriate to stop.

[Pharmacoeconomic evaluation of telbivudine vs. lamivudine in treating the patients with HBeAg-positive and negative chronic hepatitis B].

OBJECTIVE: To evaluate long-term cost effectiveness of telbivudine and lamivudine for the treatment of CHB. METHODS: Cost effectiveness was conducted from social health insurance perspective. A Markov model was established based on disease progression pattern and the data from the 2 years GLOBE clinical trial. The information of annual medical expenditure and quality-of-life assessment for different CHB-related diseases was obtained from literature. Incremental cost per life year or quality-adjusted life year gained was measured. RESULTS: Compared with lamivudine, the incremental cost for 1 additional QALY gained with telbivudine in treating HBeAg-positive and -negative CHB were 5403 yuan and 28239 yuan in Beijing, as well 4916 yuan and 29618 yuan in Guangzhou, respectively. According to national economic burden of CHB-related diseases, the ICER with telbivudine vs lamivudine were 1282 yuan and 31565 yuan for HBeAg-positive and -negative CHB. CONCLUSION: According to WHO recommendation for ICER threshold, telbivudine is cost effective in treating HBeAg-positive and -negative CHB, as compared to lamivudine.

Telbivudine: a new treatment for chronic hepatitis B.

Three hundred and fifty million people worldwide are estimated to be chronically infected with hepatitis B virus. 15%-40% of these subjects will develop cirrhosis, liver failure or hepatocellular carcinoma during their life. The treatment of chronic hepatitis B has improved dramatically over the last decade merits to the advent of nucleoside/nucleotide analogues and the use of pegylated interferons. Approved drugs for chronic hepatitis B treatment include: standard interferon-alpha 2b, pegylated interferon-alpha 2a, lamivudine, adefovir dipivoxil, and entecavir. Unfortunately, these agents are not effective in all patients and are associated with distinct side effects. Interferons have numerous side effects and nucleoside or nucleotide analogues, which are well tolerated, need to be used for prolonged periods, even indefinitely. However, prolonged treatment with nucleoside or nucleotide analogues is associated with a high rate of resistance. Telbivudine is a novel, orally administered nucleoside analogue for use in the treatment of chronic hepatitis B. In contrast to other nucleoside analogues, Telbivudine has not been associated with inhibition of mammalian DNA polymerase with mitochondrial toxicity. Telbivudine has demonstrated potent activity against hepatitis B with a significantly higher rate of response and superior viral suppression compared with lamivudine, the standard treatment. Telbivudine has been generally well tolerated, with a low adverse effect profile, and at its effective dose, no dose-limiting toxicity has been observed. Telbivudine is one of the most potent antiviral agents for chronic hepatitis B virus and was approved by the FDA in late 2006.