June 13, 2013

Eur J Gastroenterol Hepatol. 2013 Jun 6. [Epub ahead of print]

Niederau C, Mauss S, Böker K, Lutz T, Heyne R, Moog G, John C, Witthöft T, Alshuth U, Hüppe D.

aDepartment of Medicine, Katholische Kliniken Oberhausen, St Josef Hospital, Oberhausen bCenter for HIV and Hepatogastroenterology, Düsseldorf cCenter for Hepatology, Hannover dInfektiologikum Frankfurt, Frankfurt eLiver and Study Center Checkpoint fCenter of Gastroenterology, Berlin gMedical Office for Gastroenterology and Hepatology, Kassel hMedical Office for Gastroenterology and Hepatology, Stade iRoche Pharma AG, Virology, Grenzach-Wyhlen jCenter for Gastroenterology and Hepatology, Herne, Germany.

Abstract

PURPOSE: In trials of pegylated interferons (PEG-IFNs), the lack of an early virological response (EVR) was associated with sustained virological response (SVR) rates of only 0-3%. The rates were similarly low when hepatitis C virus (HCV)-RNA was positive at week 24. Treatment guidelines therefore recommend 'stop rules' on the basis of HCV-RNA levels at weeks 12 and 24 of treatment. We analyzed the use of these rules under 'real-life' conditions.

PATIENTS AND METHODS: This was a prospective, community-based cohort study involving 467 physicians from institutions throughout Germany, including 4727 treatment-naive genotype-1 patients who received a full course of treatment with PEG-IFN α-2a plus ribavirin between 2003 and 2009.

RESULTS: The overall SVR rate was 43.1%. Failure to determine EVR decreased from 20% in 2003-2004 to 10% in 2006-2007. Unexpectedly, treatment was continued in 86.1% of patients without an EVR and in those who had an EVR but were HCV-RNA positive at week 24 (67.5%), resulting in SVR rates of 15.7 and 40.9%, respectively. Between 77.5 and 95.3% of physicians did not follow prescribed recommendations to reduce PEG-IFN or ribavirin in cases of hematological abnormalities.

CONCLUSION: Although recommendations to assess EVR and HCV-RNA at week 24 were increasingly observed in daily practice, the corresponding 'stop rules' in nonresponders were neglected. The subsequent SVR was 5-10 times higher than that reported in controlled trials. This may partly be because of the fact that reductions in PEG-IFN or ribavirin dose were not performed despite recommendations. The issue of stop rules will gain even more interest since the first HCV protease inhibitors have been approved. Prolongation of treatment beyond the new stop rules is associated with risks of resistant HCV variants. Thus, the new stop rules are to be observed more strictly when compared with previous therapy with interferons and ribavirin.

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