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OBJECTIVE: To assess the cost-effectiveness of obinutuzumab (O-chemo) in comparison to rituximab (R-chemo) in patients with untreated advanced follicular lymphoma (FL) at intermediate or high risk from an Italian National Health Service (NHS) perspective. METHODS: A previously developed four-state Markov model was adapted to estimate lifetime clinical outcomes and costs of Italian patients with advanced FL and an FL international predictive index score ≥2 in treatment with O-chemo and R-chemo. Life expectancy was derived from the GALLIUM and PRIMA clinical trials. Progression-free survival (PFS), early progressive disease (PD), and treatment duration were extrapolated by fitting parametric distributions to empirical data in GALLIUM and late PD to data in PRIMA. Expected survival was weighed by published utilities. Costs updated to 2020 Euros and health gains occurring after the first year were discounted at an annual 3% rate. Probabilistic sensitivity analysis (PSA) was carried out. RESULTS: O-chemo was associated with an incremental survival increase (0.97 life-years [LYs]), even when weighted for quality (0.88 quality-adjusted LYs [QALYs]), and incremental costs (around 15,000), driven by longer treatment during PFS state relative to R-chemo. The incremental cost-effectiveness ratio and incremental cost-utility ratio are both widely accepted by the Italian NHS (around 15,500/LY and 17,000/QALY gained, respectively). PSA simulations confirmed the robustness of results given sensible variations in assumptions. CONCLUSION: O-chemo has superior clinical efficacy compared to rituximab, and should be considered a cost-effective option in first-line treatment of patients with advanced FL at intermediate or high risk in Italy. Incremental cost-effectiveness ratios are below the threshold considered affordable by developed countries.
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BACKGROUND: Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) is the most frequent and difficult-to-treat viral hepatitis worldwide. HBV DNA and hepatitis B surface antigen (HBsAg) serum levels, which help the early identification of non-responders to pegylated interferon (PEG-IFN), prompt more flexible individualized therapeutic strategies exploiting the benefits of both PEG-IFN and nucleoside/nucleotide analogues (NAs). We assessed the cost-effectiveness of week-12 HBV DNA/HBsAg stopping rule for early interruption and switch to currently most effective NA treatments (entecavir [ETV] or tenofovir disoproxil fumarate [TDF]). METHODS: A decision-analytic Markov model was developed in the following health-related states: CHB, compensated cirrhosis (CC) and decompensated cirrhosis, hepatocellular carcinoma, liver transplant, post-liver transplant, death, virological response, relapse and HBsAg clearance. Simulated strategies included: ETV/TDF in CHB; ETV/TDF delayed until CC; first-line PEG-IFN followed by switch to ETV/TDF for either patients meeting the week-12 stopping rule or week-48 null-responders/relapsers; and first-line PEG-IFN followed by switch to ETV/TDF delayed until CC. ETV and TDF were considered alternatively for a total of eight strategies. A lifetime simulation horizon was applied. RESULTS: Early treatment strategies using NAs with or without first-line PEG-IFN provided the highest results (approximately 22 life-years and 15 quality-adjusted life years [QALYs]). Delayed treatments until cirrhosis development resulted in poorer outcomes. The average per-patient lifetime costs ranged from 33,500 (TDF in CC) to 68,900 (TDF in CHB). Costs using ETV were 20-50% higher. First-line PEG-IFN strategies ranged from dominant (that is, more effective and less costly) to highly cost-effective, although differences in QALYs were always very narrow. CONCLUSIONS: The cost-effectiveness of antiviral therapy of HBeAg-negative CHB could be improved significantly using first-line PEG-IFN followed by a switch to NAs in either patients meeting the week-12 HBV DNA/HBsAg stopping rule or week-48 non-responders/relapsers.