Cost-effectiveness of tenofovir alafenamide and entecavir in chronic hepatitis B in Saudi Arabia.

Hepatitis B is a liver infection that can cause potentially life-threatening complications such as cirrhosis and hepatocellular carcinoma (HCC). An estimated 296 million people worldwide suffer from chronic hepatitis B (CHB), and 820,000 deaths were attributed to this disease in 2019 alone.[1] Thus, CHB exerts a major health and economic burden. Both entecavir and tenofovir alafenamide (TAF) are among the “preferred hepatitis B therapies” recommended by the American Association for the Study of Liver Diseases (AASLD)[2] and the Saudi Society for the Study of Liver Disease and Transplantation (SASLT) guidelines.[2,3] This editorial explores the cost-effectiveness of entecavir and TAF treatments in patients with CHB, using cost-effectiveness analysis (CEA) with a Markov state transition model. Markov models are applied in situations with ongoing continuous risk and are thus well suited for modeling diseases such as CHB. They have been applied to guide healthcare decisions and policies for various diseases including CHB. An important aspect that drives therapeutic decision-making and healthcare resource allocation is the comparative assessment of the possible health and economic impact of treatment plans. CEA is used to examine and compare the cost (economic impact) and effectiveness (health impact) of alternative treatment options. Thus, CEA can be used to decide whether a patient with CHB should be treated with entecavir or TAF. Markov models comprise one category of statistical methods that can be used for CEA. In this issue of the Journal, Sanai et al. used CEA to compare the long-term health and economic impact of switching from entecavir treatment to TAF treatment in patients with CHB in the Kingdom of Saudi Arabia (KSA).[4] The study employed a decision analytic model to simulate the course of CHB patients. The model simulated a cohort of patients with CHB and low-level viremia (LLV) while on entecavir treatment, who either remained on entecavir or were switched to TAF over a lifetime horizon. Patients entered the model at the non-cirrhosis or compensated cirrhosis state, at the time of treatment switch to TAF, and either achieved complete virologic response (CVR) or remained with LLV. The results of this study indicated that, compared to staying on entecavir, switching to TAF substantially slowed the progress of CHB and reduced the risk of death due to the disease. There was a significant reduction in the proportion of patients who progressed to advanced liver disease (5–52% reduction, based on disease stage), patients requiring liver transplants (12% reduction), and patients who died (37% reduction) in the TAF group, compared with the entecavir group. According to the base case analysis, switching to TAF compared to staying on entecavir enhanced the percentage of patients obtaining CVR (76% TAF versus 14% entecavir). In addition, switching to TAF was more cost-effective than staying on entecavir; the incremental cost-effectiveness ratio (ICER) for TAF compared with entecavir was USD 65,790 per quality-adjusted life year (QALY). Similar findings were reported from a CEA study conducted in Peru.[5] Several factors impact the cost-effectiveness of entecavir and TAF treatments for CHB. The cost of CHB treatment includes both direct medical costs, which are medication-related costs, and indirect medical costs, which are disease-related costs (such as illness-related loss of work productivity). The relative efficacy and safety of the treatments also contribute to their cost-effectiveness. The direct cost of TAF is higher than that for entecavir in most countries (total per patient direct medical costs in the KSA in 2023 for entecavir and TAF were USD 11,195 and USD 16,667, respectively[4]). The higher acquisition costs of TAF (USD 2,690) compared with continuing entecavir (USD 2,690) treatment were the primary drivers of the overall increase in total expenses. However, the impact of other factors such as indirect costs, and efficacy and safety aspects offsets the direct costs of TAF. Sanai et al.[4] did not include indirect costs in their analysis. However, disease complications and progression (such as cirrhosis and HCC) are the main factors driving these potentially substantial costs. As TAF is more effective than entecavir in reducing CHB complications and disease progression, it may be associated with lower indirect costs than entecavir. The efficacy and safety of a drug contribute significantly to its cost-effectiveness. In their pharmacoeconomic modeling study, Sanai et al.[4] found that switching to TAF increased the proportion of patients reaching CVR (TAF vs. entecavir: 76% vs. 14%) and reduced advanced liver events. In agreement with these findings, two real-world clinical studies conducted in China showed that TAF is more effective at reducing viral load in hepatitis B patients than entecavir.[6,7] These clinical data validate the findings reported by Sanai et al.[4] Additionally, TAF is also known to be safer than entecavir and is less likely to cause kidney and bone damage.[7] Consequently, TAF is more cost-effective than entecavir based on its efficacy and safety profiles as well. Hepatitis B infections exert a major health and economic burden globally. Entecavir and TAF are among the most recommended antiviral agents for treating this disease.[3] As CHB is a lifelong condition, it is important to choose the right medication. CEA is a valuable tool that can help identify the most cost-effective treatment strategy. Sanai et al.[4] created a model using real-world clinical and cost inputs from the KSA payer perspective. They sourced demographic data, transition probabilities, treatment efficacy, health state costs, and utilities using published literature relevant to KSA. Due to cost offsets brought on by a decline in advanced liver disease occurrences, switching to TAF was a more cost-effective option than staying on entecavir, despite the higher treatment costs of TAF. These findings are comparable to CEA studies conducted in various countries, indicating that TAF is more cost-effective than entecavir in treating CHB due to its superior antiviral activity, lower toxicity, and lower risk of resistance. However, the direct and indirect costs and medication availability vary according to the country and type of healthcare system. While real-world data support the findings by Sanai et al.,[4] the study itself is associated with limitations such as the inclusion of a participant population that was not KSA-specific (Asian or global), exclusive utilization of the LLV population, which limits the generalizability of the results, and the assumption that patients continued the treatment throughout their lifetime. Therefore, additional studies should be performed to evaluate the cost-effectiveness of these medications in different areas, healthcare settings, and patient populations. Following these strategies, the KSA has achieved a gradual epidemiological decrease in hepatitis B by improving its healthcare facilities. Similarly, efforts should be made to ensure that CHB patients have better access to antiviral medications worldwide, especially in low- to middle-income countries where the hepatitis B virus is endemic, and the disease burden is high. In summary, current evidence suggests that TAF may be more cost-effective than entecavir for treating CHB patients. However, the specific needs and circumstances of each patient should also be considered while deciding on the appropriate treatment. It is imperative to frame public health policies that will ensure that the most appropriate medication is easily accessible to CHB patients so that the disease burden on individuals and society may be reduced. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.