Hepatology Xagena

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Once-weekly Pegasys allows to achieve viral clearance in patients not responding to Peg-Intron in HCV patients

Final results from the REPEAT study have demonstrated that treatment with once-weekly Pegasys ( Peginterferon alfa-2a ) and daily Copegus ( Ribavirin ) can achieve viral clearance in a number of patients who did not respond to initial treatment with Peg-Intron ( Peginterferon alfa-2b ).

This outcome gives hepatitis C patients the opportunity to tackle their disease a second time after initial treatment failure. Furthermore, the results show that a patient’s response to treatment at 12 weeks is a powerful predictor of the eventual outcome: the majority of patients with undetectable virus levels at 12 weeks went on to achieve a sustained virological response ( SVR ), indicating treatment success. Few patients with detectable virus at 12 weeks achieved SVR.

Enrolling 950 patients from Europe, North America and Latin America, REPEAT ( REtreatment with PEgasys in pATients Not Responding to Peg-Intron Therapy ) was designed to explore whether intensified treatment with a higher fixed-dose induction of Pegasys and/or longer treatment duration may increase treatment success rates. Patients, who had previously not responded to at least 12 weeks of Peg-Intron plus Ribavirin combination therapy, received one of four regimens:

· Arms A and B received Pegasys 360 mcg/week for 12 weeks, followed by 180 mcg/week for a further 60 or 36 weeks, respectively,

· Arms C and D received Pegasys 180 mcg/week for 72 or 48 weeks, respectively.

All patients received Ribavirin ( 1,000/1,200 mcg/day ) in combination with Pegasys.

Results showed:

1) The primary endpoint was met: SVR, defined by undetectable hepatitis C virus RNA in the blood six months after the end of treatment, was significantly higher for arm A ( 16% ) compared to arm D ( 9% )

2) A pooled analysis of the 72-week arms vs. the 48-week arms showed that 72 weeks of treatment had the biggest impact on success of treatment, with a doubling of SVR rates compared to 48 weeks ( 16% vs. 8%, respectively ).

3) A pooled analysis of the induction dose arms versus standard dose arms showed that treatment with higher fixed-dose induction for this difficult-to-cure patient population did not provide significant additional benefit

4) Response at 12 weeks was a strong predictor of successful treatment

5) Of patients whose virus was undetectable after 12 weeks of therapy, 57% in the 72-week arms went on to achieve treatment success ( by comparison, among patients who still had detectable virus after 12 weeks, only 4% achieved treatment success )

6) The proportion of patients with undetectable virus at 12 weeks was 17%

The incidence and types of adverse events and serious adverse events were generally consistent across all the arms, and the frequency of moderate to severe hematologic effects were broadly similar. Discontinuations for adverse events and lab abnormalities were higher for extended treatment. Patients with cirrhosis had a somewhat higher incidence of adverse events, premature withdrawals and dose modifications.

Source: Roche, 2007