CCO Official Conference Coverage of the 2008 AASLD Meeting*
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4-Week Nonresponse to Peginterferon alfa/Ribavirin Predicts HCV-Infected Patient’s Failure to Achieve SVR
Posting Date: November 06, 2008
Summary of Key Conclusions
- Early (Week 4) null response in HCV-infected patients treated with peginterferon alfa/ribavirin a strong predictor of failure to achieve sustained virologic response (SVR)
- Early null response also a predictor of partial early virologic response or nonresponse at Week 12
- Suggests to consider treatment change/discontinuation in patients with early null response
Background
- Early virologic response a strong predictor of SVR in genotype 1 HCV-infected patients treated with peginterferon alfa/ribavirin
- Early detection of patients unlikely to achieve SVR possibly also beneficial
- Regimen discontinuation/change could minimize adverse effects
- Current study assessed association of early null response (eNR) (< 1 log10 decrease in HCV RNA from baseline at 4 weeks) with null response at Week 12 and with lack of SVR
Summary of Study Design
- Retrospective analysis of patients with chronic HCV infection and available Week 4 HCV RNA measurements
- Treatment must have occurred outside of clinical trials from 2005-2008
- Patients grouped according to HCV RNA decline from baseline at Week 4
- < 1 log10 reduction (eNR)
- 1 - < 2 log10 reduction
- 2 - < 3 log10 reduction
- ≥ 3 log10 reduction but HCV RNA detectable
- HCV RNA undetectable (rapid virologic response [RVR])
- Other virologic outcomes assessed
- Nonresponse at Week 12: < 2 log10 reduction in HCV RNA from baseline at Week 12
- Partial early virologic response: ≥ 2 log10 reduction in HCV RNA from baseline at Week 12, but HCV RNA still detectable
- Complete early virologic response: HCV RNA undetectable at Week 12
- SVR: HCV RNA undetectable 24 weeks posttreatment
Baseline Characteristics
- N = 159 patients
- High proportion with genotype 1 HCV infection among those who did not achieve RVR
|
Characteristic |
eNR
(n = 38) |
RVR
(n = 46) |
Neither eNR nor RVR
(n = 75) |
|
Male, % |
58 |
57 |
63 |
|
Age, yrs (range) |
53
(36-71) |
48
(20-74) |
50
(19-68) |
|
Race, % |
|
|
|
|
|
58 |
13 |
32 |
|
|
37 |
72 |
56 |
|
Genotype 1 HCV, % |
89 |
43 |
87 |
|
HCV RNA at baseline, log10 |
5.93 |
5.54 |
6.12 |
|
No previous treatment, % |
87 |
89 |
84 |
*
P < .01 for difference between groups.
Main Findings
- High rate of nonresponse and low rate of SVR at posttreament follow-up among patients with eNR
- 50% of patients with eNR had nonresponse at Week 12
|
Outcome, % |
eNR
(n = 38) |
|
Response at Week 12 |
|
|
|
50 |
- Partial early virologic response
|
39 |
- Complete early virologic response
|
3 |
|
Response at follow-up* (Week 72) |
|
|
|
71 |
|
|
8 |
|
|
8 |
*Virologic breakthrough, incomplete follow-up, discontinuation not due to nonresponse, lost to follow-up excluded from analysis.
- RVR associated with high levels of complete early virologic response and SVR
- Factors associated with Week 72 nonresponse
- Genotype 1: odds ratio [OR]: 8.77 (95% confidence interval [CI]: 2.01-38.35; P < .01)
- Log10 baseline HCV RNA: OR: 2.24 (95% CI: 1.28-3.91; P < .01)
- eNR: OR: 19.45 (95% CI: 7.85-48.21; P < .0001)
Reference
Reau N, DeVoss A, Elsen C, et al. Evaluation of early null-response (eNR) as a predictor of nonresponse to PEG RBV in patients with HCV. Program and abstracts of the 59th Annual Meeting of the American Association for the Study of Liver Diseases; October 31 - November 4, 2008; San Francisco, California. Abstract 1247.