Ribavirin Dose Reductions Due to Adverse Events Do Not Compromise Sustained Response in Some Patients

Research has shown that adequate doses of ribavirin play an important role in reducing the risk of relapse in hepatitis C patients treated with interferon-based therapy, especially those with genotype 1.

The current standard of care for chronic hepatitis C is pegylated interferon plus ribavirin, given for 24 week to patients with HCV genotypes 2 or 3 and for 48 weeks to those with hard-to-treat genotypes 1 or 4.

In the present study, reported in the January 2007 issue of Clinical Gastroenterology & Hepatology, University of Pennsylvania researchers evaluated the effect of ribavirin and pegylated interferon alfa-2a (Pegasys) dose reductions on sustained virological response (SVR) in patients with genotype 1 HCV.

Data were pooled from 569 participants enrolled in 2 Phase III trials of 48 weeks of treatment with Pegasys plus ribavirin. All patients were evaluated for the effect of cumulative drug exposure on 4- and 12-week responses. The 427 patients who completed treatment were evaluated for effect of drug exposure on SVR.

Results

• Among patients who completed therapy, more had reductions (</= 97% of  the originally prescribed cumulative dose) of ribavirin than Pegasys (43% vs 27%).
  
  
• Neither early virological response nor SVR were adversely affected by ribavirin reduction as long as the cumulative exposure was greater than 60%.
  
  
• However, the SVR rate was significantly reduced in patients with less than 60% of the intended cumulative ribavirin dose (P = 0.0006).
  
  
• Reduced SVR was associated with prolonged periods of dose reduction, temporary interruptions, or premature cessation of ribavirin.
  
  
• Ribavirin dose reduction had a minimal impact on SVR in patients who achieved rapid virological response, defined as undetectable HCV RNA after 4 weeks, even when they received less than a 60% cumulative ribavirin dose.
  
  
• In contrast, SVR was reduced markedly in patients who had ribavirin dose reductions and did not achieve rapid virological response.

Conclusion

These findings led the study authors to conclude, “Minor ribavirin dose reductions to manage adverse events do not appear to affect SVR adversely, unless cumulative exposure is less than 60%. Prospective studies, however, are required to establish the impact of ribavirin dose reduction on SVR.”

01/26/07

Reference
K R Reddy, M L Shiffman, T R Morgan, and others. Impact of Ribavirin Dose Reductions in Hepatitis C Virus Genotype 1 Patients Completing Peginterferon Alfa-2a/Ribavirin Treatment. Clinical Gastroenterology & Hepatology 5(1): 124-129. January 2007.