Appeal type: Medical Necessity
Decision: Upheld

A 48-year-old male enrollee has requested for an additional 12 weeks of Pegasys and ribavirin for treatment of his hepatitis C virus. Findings:  The physician reviewer found that the current approved treatment for hepatitis C is pegylated interferon (Pegasys) plus ribavirin for a total of 48 weeks in genotype-1 patients. Some studies have suggested that a longer treatment period may be warranted in those patients who have a late documented viral clearance while on therapy. Currently, a 12-week time point is used to determine the presence of an early viral response (EVR); however, many studies indicate that a 4-week point may also be useful in predicting a response to 48 weeks of therapy. If a patient has failed to have an EVR after 12 weeks of therapy, and there has been a major lapse in adherence to intended dosing or a prolonged treatment interruption, the clinician might wish to extend therapy for a longer time, if the clinician feels that adherence can be improved. The TeraVIC-4 study presented at the European association for the Study of Liver Diseases 2004 evaluated the treatment of patients whose HCV-RNA was positive after four weeks of treatment for a total course of either 48 weeks or 72 weeks of continued therapy. All patients were treated with pegylated interferon alfa-2a at a dose of 180 mcg per week plus ribavirin 800 mg per day; 327 patients were included in the analysis, and 90% were genotype 1. The end-of-treatment response in the group receiving 48 weeks versus the group receiving 72 weeks of therapy was 61% and 52%, respectively. The sustained viral response rate in the group receiving 48 weeks versus 72 weeks of therapy was 32% and 46%, respectively. The relapse rate in the group receiving 48 weeks versus 72 weeks of therapy was 48% and 13%, respectively.The studys authors concluded that the increased duration of therapy in this select population resulted in an increase in sustained viral response rate and a decrease in the relapse rate. There were no increased adverse events noted in the group treated for 72 weeks. Berg and colleagues also looked at relapse rates in patients treated for 48 versus 72 weeks with pegylated interferon alfa-2a 180 mcg/week plus ribavirin 800 mg per day. This study focused on the late virologic responder, which was defined as those patients whose serum HCV-RNA was positive at 12 weeks, but became negative at 24 weeks. In this particular population, there was a significant reduction in relapse rates when treatment was extended to 72 weeks. This study supports a longer duration of therapy in this patient population.In a recent prospective study to determine whether treatment extension beyond 48 weeks might benefit patients (Berg, et. al.), 230 subjects received pegylated-interferon-alfa-2a 180 mcg per week and ribavirin 800 mg per day for 48 weeks. Another group of 225 patients received the same regimen for 72 weeks. All of the subjects were treatment- naive. In the 72-week group, treatment response was seen in 71% of patients and a sustained virologic response at 24 weeks was seen in 53%. In the 48-week group, corresponding proportions were 63% and 54%. Despite the lack of significant difference, patients who were still HCV-RNA positive at week 12 showed significantly higher sustained virologic response rates when treated for 72 rather than 48 weeks (29% versus 17%). The team concluded that extended therapy should be reserved for patients `with slow virologic response defined as HCV-RNA positive at week 12 but negative at week 24.`Based on these studies, even though some experts are of the opinion that patients who are intrinsically resistant to treatment and are late responders should be continued on therapy for an additional 36 weeks after they first become aviremic, this extended duration of treatment is considered investigational/experimental, and not a standard of care at the present time.