 |
|
|
| |
Double-Dose Peginteferon Alfa-2b (pegIntron) Plus Weight-Based Ribavirin for Re-Treatment of African-american Non-Responders with Hepatitis C
|
| |
| |
Reported by Jules Levin
JB Gross1, SM Johnson1, TH Therneau1, PY Kwo2, Raie R3, Rubin RA4, Bruno CJ4, IM Jacobson5, NH Afdahl6, and the RENEW Invstigators
1Mayo Clinic College of Medicine, Rochester, MN
2Indiana University Medical Center, Indianapolis IN
3Johns Hopkins Medical Center, Baltimore MD
4Emory University Medical Center, Atlanta GA
5New York Presbyterian Hospital, New York NY
6Beth Israel deaconess Medical center, Boston MA
John Gross presented this interesting data at a HCV oral session at DDW.
At the 55th AASLSD Nov 2004, Diago et al presented this pilot study data on high dose Pegasys induction dosing suggesting that high dose Pegasys induction is a treatment option for IFN/RBV non-responders. I believe Roche is planning a followup study:
Pilot Study, Hi-Dose Pegasys Induction- 37% SVR for IFN/RBV Nonresponders
http://www.natap.org/2004/AASLD/aasld_21.htm
Before reporting on this article, there was a report at this DDW finding that prolonged HCV therapy was not beneficial. These findings are in conflict with previously reported findings at Nov 2004 AASLD, which I find as being better research so here is link to these AASLD reports:
Prolonged Pegasys+RBV Therapy to 72 Weeks May Improve SVR in Patients Who were HCV RNA+ after 4 weeks & slow responders
http://www.natap.org/2004/AASLD/aasld_25.htm
Studies have found lower SVR response rates for African-Americans than for Caucasians. Here are links to several published studies. The Jeffers Pegasys study found 26% SVRs for African-Americans receiving Pegasys for first-time therapy. The PegIntron study found a 19% SVR for first-time therapy for African-Americans.
Pegasys plus Ribavirin for African-Americans with Genotype 1
"Peginterferon alfa-2a (40 kd) and ribavirin for black American patients with chronic HCV genotype 1"
Hepatology, June 2004
http://www.natap.org/2004/HCV/060104_03.htm
PegIntron (Peginterferon Alfa-2b) and Ribavirin for the Treatment of Chronic Hepatitis C in Blacks and Non-Hispanic Whites
New England Journal of Medicine, May 2004
http://www.natap.org/2004/HCV/060104_06.htm
Here is link to article that reviews comprehensively I think the mainstream & non-mainstream potential reasons for lower response rates for African-Americans to HCV therapy with PegIFN/RBV:
Hepatitis C Virus Among African-American Persons
Current Hepatitis Reports Jan 2004
http://www.natap.org/2005/HCV/011205_06.htm
Back to DDW Gross study report
The RENEW Trial (RE-treatment of Non-responders with Escalating Weight-based Therapy) is a large trial in the USA at about 100 academic & community centers, IFN/RBV nonresponders only, retreated with PegIFN a-ab+RBV. The trial is completed, final analysis is pending. Gross presented a sub-group analysis of only African-American participants. Several studies have reported in the past year that only 12% of IFN/RBV non-responders achieve SVR with PegIFN/RBV. Of course this response rate varies depending on a patient’s individual characteristics; for example, genotype 1 patients have lower response compared to genotype 2/3.
RENEW TRIAL AIMS
The purpose of this study was to determine whether doubling the dose of peginterferon a-2b, together with weight-based RBV improves re-treatment response rates. And, to assess the safety & tolerability of high-dose peginterferon plus ribavirin.
Patients received peginterferon 1.5 ug/kg or 3.0 ug/kg once weekly by subcutaneous injection along with ribavirin 12-15 mg/kg (weight-based dosing), for 48 weeks treatment; SVR was evaluated after a 24 week followup period, total 72 weeks.
Doses were reduced 33% for toxicity.
Growth factors were not used.
Intent-To-Treat Analysis.
963 patients enrolled in study.
152 African-Americans: 66 recd 1,5 ug/kg (11 did not start treatment), 64 recd 3.0 ug/kg (6 did not start treatment). (22 recd 0.5 ug/kg, this arm was discontinued).
RESULTS
SVR:
16% (3.0 ug/kg, high dose)
4% (1.5 ug/kg, standard dose) p=0.04
After 24 weeks, HCV negative: 26% vs 16%; after 48 weeks: 16% vs 9%. So there was no relapse in the high dose arm.
TOLERABILITY
Dose reduction in 1st 12 weeks:
26% in 3.0 ug/kg dose group
20% in 1.5 ug/kg
Dose reduction overall:
33% in 3.0 ug/kg
36% in 1.5 ug/kg
Discontinued for AE:
11% for 3.0 ug/kg
15% for 1.5 ug/kg
LEUKOCYTE COUNTS
Gross showed a graph in his talk showing that these counts were about the same for both dose groups but appeared slightly lower for the 1.5 ug/kg dose group. After treatment stopped both groups counts increased back towards baseline. At baseline WBC (1000 per mcL) was about 6 for both groups & at 48 weeks both groups were about 3.
In summary, Gross said high body weight did not effect the outcome, using weight-based treatment regimen. In a patient group with an inherently low response rates, aggressive dosing can achieve a re-treatment response rate comparable to other patient groups. High dose regimens should be explored further in patient populations with low response rates to standard peginterferon/ribavirin HCV therapy.
|
|
| |
| |
|
|
|
|
|
