By Liz Highleyman

It is known that a wide variety of factors can influence the success of hepatitis C treatment with pegylated interferon plus ribavirin. Several analyses of data from the large WIN-R trial explored some of these factors: presence of fibrosis or cirrhosis, cigarette smoking, HCV RNA level, and providers’ experience in treating hepatitis C.

WIN-R included 4913 participants who were randomly assigned to received pegylated interferon alfa-2b (Peg-Intron) with either 800 mg fixed dose ribavirin or weight-based doses ranging from 800 mg to 1400 mg. Patients with genotype 1 HCV were treated for 48 weeks; those with genotype 2 or 3 were randomized again to receive either 24 or 48 weeks of therapy.

As previously reported, one study found that cirrhosis - but not fibrosis - was associated with lower sustained response rates (DDW abstract 655)
http://www.hivandhepatitis.com/2006icr/ddw/docs/052306_e.html

Cigarette Smoking

Another analysis looked at the effect of tobacco smoking, which in prior studies has been associated with increased liver inflammation and fibrosis in people with hepatitis C. At enrollment in WIN-R, participants were asked whether they were smokers or non-smokers. Smoking data was available for 2865 out of 4223 patients (68%) included in the primary efficacy analysis; of these, 894 (31%) were smokers and 1971 (69%) were non-smokers.

 Sustained virological response (SVR) rates for smokers and non-smokers, broken down by genotype (1 vs 2/3) and fixed (FD) or weight-based dosing (WBD), are shown in the table below:

Tobacco smokers with genotype 2 or 3 HCV had significantly lower SVR rates than non-smokers. However, this difference was not observed among genotype 1 patients.

The researchers recommended that additional studies be conducted to further explore how cigarette smoking influences treatment response and the effect of smoking cessation prior starting hepatitis C therapy.

High Viral Load

In another study, researchers stratified genotype 1 WIN-R participants on the basis of pretreatment HCV viral load.

Out of the total 4913 study subjects, 3018 had genotype 1 HCV. The overall SVR rate in this group was 33%. However, those who started treatment with a low viral load (< 2 million copies/mL) had a significantly higher SVR rate than those with higher baseline viral loads (35% vs 31%, respectively).

As shown in the table below, SVR rates appeared to increase among patients with viral loads of 15-30 million copies/mL, although these differences were not statistically significant. The researchers concluded that, “Within the genotype 1 patient population with high viral load as defined traditionally (≥ 2 million copies/mL), those with very high viral loads do not have impaired rates of SVR.”

Prior Treatment Experience

Finally, a third analysis looked at the impact of providers’ prior experience in treating hepatitis C. The point of this study was to explore whether sustained response rates seen in clinical trials conducted in academic settings could be replicated in community-based practice.

WIN-R was conducted at 225 study sites, including both academic and community settings. Researchers at 25 sites who had prior experience conducting HCV trials or extensive experience treating hepatitis C were designated as regional principal investigators (PIs).

Of the 4913 total WIN-R participants, 923 (19%) were treated at regional PI sites and 3990 (81%) were seen at non-regional PI sites. Sites with more than 25 patients had some of their data verified by study monitors; 3114 participants (63%) were treated at monitored sites. Overall, 1800 patients (37%) dropped out before the end of the study.

The authors concluded that patients treated at regional PI sites were more likely to achieve SVR, and less likely to drop out compared with participants seen at the non-regional PI sites. However, no differences in SVR or drop-out rates were observed between monitored or non-monitored sites.

These data may shed light on some past research showing that SVR rates in community clinic settings are lower than those obtained in clinical trials, and point to the need for ongoing education of providers about advances in hepatitis C treatment.

6/02/06

References

M.P. Pauly, A.J. Sheinbaum, J. Szpakowski, and others. The influence of cigarette smoking on response to treatment with pegylated interferon alfa-2b and ribavirin in patients with chronic hepatitis C. Abstract S1923. DDW 2006. May 20-25, 2006. Los Angeles, CA.

I.M. Jacobson, R.S. Brown, B. Freilich, and others. Stratification of high viral load: impact on sustained virologic response in the WIN-R trial. Abstract T1806. DDW 2006. May 20-25, 2006. Los Angeles, CA.

P. Kwo, I. Jacobson, R. Brown, and others. Prior HCV treatment experience and its relationship to sustained virologic response (SVR): an analysis of the WIN-R study database, a US academic community-based trial. Abstract T1802.