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Peginterferon alfa-2a (PEGASYS) plus ribavirin (COPEGUS) for 16 or 24 weeks in patients with HCV genotype 2 or 3
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Final results of the ACCELERATE trial
Mitchell L. Shiffman, MD
on behalf of the ACCELERATE study investigators
Virginia Commonwealth University Medical Center, Richmond, VA, USA
Reported by Jules Levin
EASL, April 29, 2006, Vienna, Austria
AUTHOR CONCLUSIONS
The overall results of ACCELERATE, the largest study ever conducted in HCV genotype 2/3 patients, have demonstrated that 16 weeks of treatment is inferior to the current standard of care, 24 weeks of treatment
A significantly higher SVR rate was observed with
24 weeks compared with 16 weeks of treatment, irrespective of
- HCV genotype infection
- RVR status
- Baseline serum HCV RNA level
The lower SVR in patients treated for 16 weeks in ACCELERATE was secondary to a near doubling in the relapse rate.
An increase in the relapse rate was also observed in previous studies when the duration of therapy was reduced1-3
Genotype 2/3 patients without an RVR have an SVR rate of only 49%
- This SVR rate after 24 weeks' therapy is similar to that seen previously in genotype 2/3 patients without an RVR (48%)2
- The possibility that SVR can be increased by treating these patients for 48 weeks needs to be explored in a prospective controlled trial
1Dalgard O, et al. Hepatology 2004; 40: 1260-5
2Mangia A, et al. NEJM 2005; 353: 2609-17
3von Wagner M, et al. Gastroenterology 2005; 129: 522-7
BACKGROUND and AIM
- The current standard of care for patients with HCV genotype 2/3 infection is a pegylated IFN + RBV (800 mg/day) for 24 weeks1
- Based on data from a large phase III randomized trial of Peg-IFN alfa-2a (PEGASYS) + RBV (COPEGUS)2 showing similar SVR rates with 24 and 48 weeks of treatment in genotype 2/3 patients
- SVR rates of >80% with this treatment has led to studies investigating whether an even shorter duration of treatment can yield similarly high SVR rates
1Strader DB, et al. Hepatology 2004; 39: 1147-71
2Hadziyannis SJ, et al. Ann Intern Med 2004; 140: 346-55
- Several small studies have suggested that a shorter duration of treatment (12-16 weeks) may be sufficient in a subset of HCV genotype 2/3 patients1-3
- Patients with an RVR (rapid viral response: undetectable HCV RNA after 4 weeks treatment)
- Limitations of these prior studies
- Not all randomized and controlled
- Relapse rates increased with shorter treatment durations
- Unable to exclude inferiority due to small sample size
- ACCELERATE, the largest ever trial in HCV genotype 2/3 patients was performed to definitively determine whether a 16-week course of Peg-IFN alfa-2a + RBV is as effective as the current recommended duration of 24 weeks
1von Wagner M, et al. Gastroenterology 2005; 129: 522-7
2Dalgard O, et al. Hepatology 2004; 40: 1260-5
3Mangia A, et al. NEJM; 353: 2609-17
STUDY DESIGN
PATIENTS
- HCV genotype 2 or 3 infection
- Treatment naive
- Age >18 years
- HCV RNA (>600 IU/mL; COBAS AMPLICOR HCV Monitor Test, v2.0) in serum
- Elevated ALT
- Liver biopsy consistent with a diagnosis of CHC within 24 months of study start
- Compensated liver disease (Child-Pugh Grade A)
STATISTICAL ASSUMPTIONS
Treatment with Peg-IFN alfa-2a + RBV for 16 weeks is no worse than treatment with Peg-IFN alfa-2a + RBV for 24 weeks by more than 6% in the rate of SVR.
Non-inferiority design
- ITT analysis would bias results in favor of a shorter treatment duration (drop-out at week 16 with unblinding).
- A more stringent per protocol analysis (standard analysis) was performed.
- Standard population included all patients treated without major protocol violations or deviations.
Baseline characteristics
The cirrhosis rates are high at 20-28% as you can see in the table, and may have something to do with 16 weeks therapy being less effective.
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