Entecavir Monotherapy Research Articles

Cost Effectiveness of Entecavir versus Lamivudine with Adefovir Salvage in HBeAg-Positive Chronic Hepatitis B

To evaluate the cost effectiveness of treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with entecavir compared with lamivudine with adefovir salvage, based primarily on the results of a recent 2-year, randomised, multicentre, clinical trial (n = 709). Previous economic analyses have been limited by the lack of comparative clinical data for entecavir and lamivudine beyond 1-year duration and for salvage therapy. We conducted a cost-utility analysis using a Markov model from a US-payer perspective over a lifetime time horizon. The hypothetical cohort was 35-year-old patients with HBeAg-positive CHB. We evaluated 2 years of treatment with entecavir 0.5mg/day versus lamivudine 100mg/day, plus addition of adefovir 10mg/day for patients who developed virologic breakthrough due to resistance to either drug. In a scenario analysis, we considered adefovir plus lamivudine combination therapy for treatment-naive patients. Clinical and economic inputs ($US, year 2006 values) were derived from publicly available data, and probabilistic sensitivity analyses were conducted to evaluate uncertainty in the results. The estimated 10-year cumulative incidence of cirrhosis for patients initiated on entecavir was 2.3% lower than for those on lamivudine (20.5% vs 22.8%). The discounted incremental cost per QALY gained was $US7600 in the base-case analysis, and the 95% central range from probabilistic sensitivity analysis was $US2500-$US19 100. Combination therapy for treatment-naive patients led to an increase in costs without improvement in patient outcomes compared with entecavir monotherapy. Our analysis suggests entecavir improves health outcomes in a cost-effective manner compared with lamivudine with adefovir salvage or combination therapy, and highlights the importance of using evidence-based effectiveness estimates in economic studies of CHB therapies.

Treatment Alternatives for Hepatitis B Cirrhosis: A Cost-Effectiveness Analysis

Hepatitis B virus (HBV) patients with cirrhosis are at risk for developing costly, morbid, or mortal events, and therefore need highly effective therapies. Lamivudine is effective but is limited by viral resistance. In contrast, adefovir and entecavir have lower viral resistance, but are more expensive. The most cost-effective approach is uncertain. We evaluated the cost-effectiveness of six strategies in HBV cirrhosis: (1) No HBV treatment ("do nothing"), (2) lamivudine monotherapy, (3) adefovir monotherapy, (4) lamivudine with crossover to adefovir on resistance ("adefovir salvage"), (5) entecavir monotherapy, or (6) lamivudine with crossover to entecavir on resistance ("entecavir salvage"). The primary outcome was the incremental cost per quality-adjusted life-year (QALY) gained. The "do nothing" strategy was least effective yet least expensive. Compared with "do nothing," using adefovir cost an incremental US dollars 19,731. Entecavir was more effective yet more expensive than adefovir, and cost an incremental US dollars 25,626 per QALY gained versus adefovir. Selecting between entecavir versus adefovir was highly dependent on the third-party payer's "willingess-to-pay" (e.g., 45% and 60% of patients fall within budget if willing-to-pay US dollars 10K and US dollars 50K per QALY gained for entecavir, respectively). Both lamivudine monotherapy and the "salvage" strategies were not cost-effective. However, between the two salvage strategies, "adefovir salvage" was more effective and less expensive than "entecavir salvage." Both entecavir and adefovir are cost-effective in patients with HBV cirrhosis. Choosing between adefovir and entecavir is highly dependent on available budgets. In patients with HBV cirrhosis with previous lamivudine resistance, "adefovir salvage" appears more effective and less expensive than "entecavir salvage."

New developments in the treatment of chronic hepatitis B

Significant progress has been made during the last 2 years in the treatment of chronic hepatitis B (CHB). Treatment decisions differ significantly depending on whether patients are HBeAg+ or HBeAg-, treatment-naive or nucleoside/nucleotide-resistant, and in early or advanced stages of liver disease. Courses of finite duration, aiming to achieve sustained off-therapy responses, are practically restricted to HBeAg+ patients with compensated chronic liver disease, whereas long-term therapy aiming to achieve maintained on-therapy remission is mostly applicable to HBeAg- individuals either with early or advanced liver disease. A course of finite duration with pegylated (PEG)-IFN-α-2a offers the highest probability of sustained off-therapy response in HBeAg+ individuals, as well as in some HBeAg- individuals. Long-term therapy with nucleoside/nucleotide analogues, both in HBeAg+ and HBeAg- CHB, has most favourable effects on patient outcome, provided that virological and biochemical remission is maintained without development of viral resistance. The best results are achievable with potent analogues suppressing serum hepatitis B virus (HBV) DNA to non-detectability by most sensitive techniques. The best 2-year resistance profile has hitherto been reported with entecavir monotherapy, and the best long-term resistance profile was seen with adefovir of 5-year duration. Adefovir is effective in most lamivudine (LAM)-resistant patients, but should be administered as an add-on rather than as a substitute for LAM. Combination therapies have entered the treatment arena of CHB by the side doors of LAM-resistance and of end-stage liver disease, and the most recent results suggest that treatment with combinations of two strong nucleosides/nucleotides with different resistance profiles may turn out to be the optimal first-line/first choice option in CHB.