Individually Tailored Duration of Hepatitis C Treatment Does Not Improve Virological Response

		SUMMARY: Tailoring the duration of interferon-based therapy on an individual basis according to early viral kinetics -- or how long it takes to first reach an undetectable HCV viral load -- did not lead to improved outcomes in people with genotype 1 chronic hepatitis C, according to a study in the August 2009 issue of Hepatology.

By Liz Highleyman

While treatment for chronic hepatitis C virus infection has improved markedly in recent years, about half of patients with hard-to-treat HCV genotype 1 still do not achieve a sustained virological response (SVR) -- or cure -- using current standard therapy, which consists of pegylated interferon plus ribavirin for 48 weeks. Therefore, researchers have explored alternative strategies for optimizing treatment, including variable durations of therapy.

In the present study, 433 genotype 1 chronic hepatitis C patients were randomly assigned to receive either a standard regimen of 1.5 g/kg/week pegylated interferon alfa-2b (PegIntron) plus 800-1400 mg/day weight-adjusted ribavirin for 48 weeks (Group A; n = 225), or else an individually tailored duration regimen lasting between 18 and 48 weeks (Group B; n = 208). In Group B, the length of therapy was calculated as the time it took to first reach undetectable HCV RNA using a bDNA assay (limit of detection 615 IU/mL) multiplied by 6.

Results

	Sustained virological response rates, assessed 24 week after completing therapy, were significantly lower in the tailored duration group compared with the standard duration group (34.6% vs 48.0%, respectively; P = 0.005).
	The difference reflected a higher relapse rate in the variable duration group (32.7% vs. 14.2% respectively; P < 0.0005).
	Baseline viral load and time to reach undetectable HCV RNA using a more sensitive TMA assay (limit of detection 5.3 IU/mL) were significant predictors of sustained response.
	In an analysis of patients with both low baseline HCV viral load (< 800,000 IU/mL) and a negative TMA test within the first 4 weeks of treatment, SVR rates were comparable in the standard and tailored duration groups.
	Within this group, even patients treated for only 18 or 24 weeks had a SVR rate above 80%.

"The individualized treatment strategy according to time to bDNA negativity failed to provide comparable efficacy compared with the standard of care," the study authors concluded. "The inferiority of the individualized protocol may be explained by the use of a less sensitive HCV RNA assay, and also by underestimation of the importance of baseline viremia."

Universitätsklinikum Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany; Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe Universität Frankfurt a.M., Frankfurt, Germany; Medizinische Klinik und Poliklinik II der Universität Würzburg, Würzburg, Germany; Hepatologische Schwerpunktpraxis Charlottenburger Str., Berlin, Germany; Medizinische Universitätsklinik Freiburg, Freiburg, Germany; Klinikum der Christian-Albrechts-Universität, Kiel, Germany; Klinikum Grosshadern, Ludwig-Maximilians-Universität, München, Germany; Medizinische Universitätsklinik II, Bonn, Germany; Medizinische Universitätsklinik Eppendorf, Hamburg, Germany; Essex Pharma GmbH, München, Germany; Charité, Institut für Biometrie und Klinische Epidemiologie, Berlin, Germany.

10/30/09

Reference
T Berg, V Weich, G Teuber, and others. Individualized treatment strategy according to early viral kinetics in hepatitis C virus type 1-infected patients. Hepatology 50(2): 369-377. August 2009. (Abstract).