Duration of Pegylated Interferon plus Ribavirin May Be Tailored Based on Early P

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Duration of Pegylated Interferon plus Ribavirin May Be Tailored Based

on Early Patient Response

By Liz Highleyman

Evidence continues to accumulate showing the benefits of individually

tailored treatment for hepatitis C. Two recent studies looked at

longer and shorter durations of combination therapy with pegylated

interferon plus ribavirin.

Longer Treatment for Slow Responders

In the first study, researchers assessed whether a longer course of

therapy would lead to a higher sustained virological response (SVR)

rate in patients classified as " slow responders. " Results were

published in the December 2007 issue of Hepatology and presented at

the 58th Annual Meeting of the American Association for the Study of

Liver Diseases in Boston (November 2-6, 2007).

Study participants were treatment-naive slow responder U.S. patients

with chronic genotype 1 hepatitis C. Slow response was defined as

achieving at least a 2-log reduction in HCV RNA from baseline, still

having detectable HCV viral load at week 12, but undetectable HCV RNA

at week 24 (limit of detection 10 IU/mL). About half the participants

were African-American.

All participants were treated with 1.5 mcg/kg/week pegylated

interferon alpha-2b (PegIntron) plus 800-1400 mg/day ribavirin. They

were randomly assigned in a 1:1 manner to complete 48 weeks (standard

of care) or 72 weeks of therapy.

Results

• End-of-treatment response rates were similar in the 48-week and 72-

week groups (45% versus 48%; P = non-significant).

• The overall SVR rate was greater in patients treated for 72 weeks

versus 48 weeks (38% versus 18%, respectively; P = 0.026).

• Dose reductions and treatment discontinuations due to adverse

events or laboratory abnormalities were similar in the 2 treatment

arms.

" Extending the treatment duration from 48 weeks to 72 weeks in

genotype 1-infected patients with slow virologic response to

peginterferon alpha-2b and weight-based ribavirin significantly

improves SVR rates, " the researchers concluded. " Treatment extension

does not seem to increase the rate of dose reduction or therapy

discontinuation. "

While the end-of-treatment response rates were comparable in the 2

duration arms, slow responders who received extended therapy were

less likely to experience relapse after completing therapy.

Treatment Length Based on Rapid Response

In the second study, Italian researchers tested the hypothesis that

variable treatment duration individualized on the basis of first

undetectable HCV RNA is as effective as standard 48-week treatment.

This study included 696 genotype 1 chronic hepatitis C patients

treatment with either 180 mcg/week pegylated interferon alfa-2a

(Pegasys) or 1.5 mcg/kg/week PegIntron plus 1000-1200 mg/day

ribavirin. One group (n = 237) was treated for the standard 48-week

duration. The other group (n = 459) received variable durations of

treatment based on early response:

• 24 weeks if HCV RNA became undetectable at 4 weeks;

• 48 weeks if HCV RNA became undetectable at 8 weeks;

• 72 weeks if HCV RNA became undetectable at 12 weeks.

Results

• 45% of patients in the standard duration group and 49% in the

variable duration group achieved SVR (P = 0.37).

• 27% first achieved undetectable HCV RNA at 4 weeks, 28% at 8 weeks,

and 11% at 12 weeks.

• In the standard duration group, 87%, 70%, and 38% of patients who

first achieved undetectable HCV RNA at 4, 8, and 12 weeks,

respectively, achieved SVR.

• In the variable duration arm, the corresponding SVR rates were 77%,

72%, and 64%.

• Low baseline HCV RNA levels and younger age were independent

predictors of rapid virological response (RVR) at week 4.

• Patients with RVR who had a high baseline viral load & #8805; 400,000

IU/mL had a higher SVR rate when treated for 48 rather than 24 weeks

(87% vs 73%; P = 0.14).

• The only predictive factor for SVR in patients with RVR was

advanced liver fibrosis.

In conclusion, the authors wrote, " Variable treatment duration

ensures SVR rates similar to those of standard treatment duration,

sparing unnecessary side effects and costs. "

01/04/08

References

BL Pearlman, C Ehleben, and S Saifee. Treatment extension to 72 weeks

of peginterferon and ribavirin in hepatitis C genotype 1-infected

slow responders.Hepatology 46(6): 1688-1694. December 2007.

BL Pearlman and C Ehleben. Improved Response Rates with Treatment

Extension to 72 weeks in Slow Responders to Peginterferon and Weight-

Based Ribavirin in Chronic Hepatitis C Virus (HCV) Infection. 58th

Annual Meeting of the American Association for the Study of Liver

Diseases. Boston, MA, November 2-6, 2007. Abstract 265.

A Mangia, N Minerva, D Bacca, and others. Individualized treatment

duration for hepatitis C genotype 1 patients: A randomized controlled

trial. Hepatology 47(1): 43-50. January 2008.