Cost-Effectiveness in Hepatitis B

IN RESPONSE:

Drs. Weitzman and Jacobson identify some key issues in the management of chronic HBV infection in an era where several agents are now licensed for this indication. In particular, both entecavir and pegylated interferon have been approved for chronic HBV infection since our manuscript was accepted for publication. Our model did not include these agents. Drs. Weitzman and Jacobson rightfully point out that the effectiveness of entecavir is diminished in the presence of lamivudine resistance, arguing that this finding should dissuade clinicians from using lamivudine as a first-line agent. We agree that this observation should give pause to routinely using lamivudine to treat chronic HBV infection. However, our model evaluated “adefovir salvage therapy” (that is, using up-front lamivudine followed by adefovir in case of resistance), not “entecavir salvage therapy.” Our systematic review of the literature (published as an online appendix with the manuscript) found no published data to support a decrement in the effectiveness of adefovir in the presence of lamivudine resistance. Therefore, we believe that our results regarding adefovir salvage therapy are valid. In contrast, it seems unlikely that entecavir salvage therapy will be cost-effective, mainly because of the data highlighted by Drs. Weitzman and Jacobson. Furthermore, the higher price of entecavir (its current average wholesale price is roughly 20% higher than that of adefovir) may not offset its low rate of viral resistance, and up-front entecavir therapy may ultimately be less cost-effective than competing, less expensive therapies.

In addition, we must recognize the difference between patients without evidence of advanced fibrosis or cirrhosis (the subject of our analysis) and those with more advanced disease. In patients without advanced disease, viral progression is slow, poor outcomes are infrequent, and overall survival rates are not different from those of matched controls without chronic HBV infection. This is not an argument to avoid treatment but instead underscores the importance of rational therapeutic decision making in the face of health economic realities. In cases of cirrhosis or advanced fibrosis (health states plagued by the specter of impending clinical complications), patients may develop resource-intensive, morbid, or fatal complications in short order. Although antiviral resistance is never a goal of therapy in either group of patients, the development of resistance has less severe health economic consequences in noncirrhotic patients than in those with the disease who can ill afford the emergence of viral resistance and subsequent viral flares.

In short, our analysis only applies to patients without advanced disease and cannot be generalized to telbivudine, entecavir, or pegylated interferon therapies. We agree that future analyses must account for these newer agents. As data evolve, the results of future models may indeed marginalize lamivudine in lieu of alternative agents. Until then, we are left with the constant presence of health economic restraints and the fact that most HBV-infected patients without cirrhosis never develop complications of chronic liver disease. These factors preclude any cut-and-dried proclamations about how best to treat noncirrhotic HBV infection in a resource-limited environment. We look forward to updating our model to reflect emerging data in this rapidly changing field.