How Effective Is Pegylated Interferon plus Ribavirin for HCV Genotype 1 Patients Over Age 50?

The prognosis of patients with chronic hepatitis C is influenced by viral factors such as HCV genotype and HCV RNA level, as well as patient factors such as age, sex, race, presence of cirrhosis, and adherence to therapy.

The demographics of HCV infection have shifted in recent years, and an increasing number of chronic hepatitis C patients now in their 50’s.

To assess the impact of age on sustained virological response (SVR) rates, researchers analyzed the data from 2 large phase III studies of pegylated interferon alfa-2a (Pegasys) plus ribavirin (Fried et al. NEJM 2002 and Hadziyannis et al. Ann Intern Med 2004). Results were reported at the 58th Annual Meeting of the American Association for the Study of Liver Diseases in Boston (November 2-6, 2007).

The investigators included patients with HCV genotype 1 who were randomized to 48 weeks of treatment with 180 mcg/week Pegasys plus 1000-200 mg/day ribavirin. SVR was defined as undetectable HCV RNA by qualitative PCR 24 weeks after completion of treatment.

 
Results

Overall, the SVR rate was 52.3% in patients < 50 years (n=438) and 38.9% in patients > 50 years (n=131) (P = 0.007).

SVR rates in patients aged > 50 years were heterogeneous and varied according to previously well-established prognostic factors (see table).

In particular, SVR rates were higher in patients without advanced fibrosis, those with low baseline HCV RNA levels, those who received >8 0% of the planned Pegasys dose, and those who received > 60% of the planned ribavirin dose.

On the whole, age did not influence whether patients completed therapy (75.6% of patients < 50 vs 73.3% of patients > 50; P = 0.5954).

However, there was a trend towards lower cumulative Pegasys exposure among older patients (7235 mcg in patients < 50 vs 6868 mcg in patients > 50; P = 0.0986).

There was a significantly lower cumulative ribavirin exposure in older patients (304 g in patients < 50 vs 252 g in patients > 50; P < 0.0001).

More patients > 50 years had dose reductions resulting in < 60% of target ribavirin exposure than patients < 50 years (38% vs 22%); decreasing ribavirin exposure to < 60% of the target dose has previously been associated with a dramatic reduction in SVR (Reddy et al. Clin Gastro Hepatol 2007).

Discontinuation rates due to any adverse event were similar in patients < 50 (11.4%) and those > 50 years old (11.5%).

Conclusion

In conclusion, the study investigators wrote, “SVR rates in certain subgroups (those without advanced fibrosis, low HCV RNA levels) of older patients are comparable to younger patients, especially if high rates of adherence can be maintained.”

They also noted that although ribavirin dose reductions were more common in chronic hepatitis C patients older than 50 years of age, “these patients can be effectively treated.”

Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA; 2Ist GmbH, Mannheim, Germany; Roche, Basel, Switzerland; Henry Dunant Hospital, Athens, Greece.

This research was funded by Roche, Basel, Switzerland.


R Reddy, D Messinger, M Popescu, and others. High rates of sustained virologic response (SVR) in patients >50 years infected with HCV genotype 1 with positive prognostic factors treated with peginterferon alfa-2a (40KD) (Pegasys) and ribavirin (Copegus). 58th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, MA, November 2-6, 2007. Abstract 321.