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Consensus Interferon in Peg/RBV Relapsers & Nonresponders in Dallas: 48 weeks end of treatment viral response
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"Consensus Interferon Plus Ribavirin Therapy: End of treatment Viral Response in Patients who were Nonresponders or Relapsers to Prior PegIFN plus Ribavirin Therapy in the USA"
Authors: Reem Ghalib et al. The Liver Institute at Methodist Dallas, Texas
Reported by Jules Levin
DDW, May 2006, Los Angeles
This report contains all information and data presented in the poster at DDW. It's a small retrospective study but is conducted in an American population. This study is one of a number of small studies including the German studies conducted by Kaiser. As you may know a large phase III study of Consensus Interferon is ongoing, from which we should be able to better understand the utility of Consensus Interferon.
STUDY DESIGN & SUMMARY OF RESULTS
Retrospective all-comers cohort study in 1 clinic (growth factors allowed); 49 patients (30 peg/RBV non-responders & 19 peg/RBV relapsers) received Consensus Interferon (Infergen) 15 mcg QD (once daily) plus ribavirin 11 mg/kg/day for 48 weeks with a 24-week follow-up.
Aims
_ To describe the on treatment viral response to consensus interferon (CIFN) plus ribavirin combination therapy in patients who were nonresponders or
relapsers to prior treatment with PEG INF plus ribavirin therapy for chronic hepatitis C (HCV).
_ Viral Response during treatment at
- Week 4
- Week 12
- Week 24
- Week 48
Study Design
_ Retrospective cohort analysis of chronic HCV patients in our clinic who are on treatment or have been treated with consensus interferon plus ribavirin therapy.
_ This is an all-comers study including all patients of any genotype who are nonresponders or relapsers to prior Peg IFN plus RBV therapy and began treatment with consensus interferon plus ribavirin
_ Growth factors were allowed in this study
_ Patients were discontinued from treatment if they had < 2 log decrease in viral count at week 24 of treatment
_ Inclusion:
- Prior treatment with at least 12 weeks of an adequate dose PEG IFN plus ribavirin therapy
- Began treatment with consensus interferon (15 mcg sq per day) plus ribavirin therapy (weight based)
- Either discontinued treatment with consensus interferon plus ribavirin or completed at least 48 weeks therapy
_ Exclusion:
- Decompensated liver disease patients
AUTHOR CONCLUSIONS
In nonresponders and relapsers to prior PEG IFN plus ribavirin therapy, the virologic response rates (<5 IU/mL) at week 48 with consensus interferon (CIFN) 15 mcg daily plus weight based ribavirin therapy were 30% and 79%, respectively.
Patients with genotype 1 vs. non-1 at week 48 had undetectable virus in 22% and 100% of nonresponders and 69% and 100% of relapsers, respectively.
In non-African Americans undetectable virus at week 48 was found in 42%
and 78% in nonresponders and relapsers, respectively.
CIFN plus ribavirin therapy was well tolerated in this population with 71% continuing treatment beyond week 24 (60% in nonresponders and 89% in relapsers). Twenty-five patients (51%) completed 48 weeks of treatment (33% in nonresponders and 79% in relapsers).
Further investigation of predictive factors of sustained viral response is needed in
the nonresponder and relapser population to guide selection of appropriate treatment candidates and therapies.
SUMMARY OF RESULTS (more detailed results follow below)
_ Week 4 Evaluation (5 patients not tested):
HCV RNA negative (<5 IU/mL):
- 2/30 (7%) of prior nonresponders vs.
6/19 (32%) of prior relapsers (p= 0.045)
_ Week 12 Evaluation:
HCV RNA negative (<5 IU/mL):
- 7/30 (23%) of prior nonresponders vs.
12/19 (63%) of prior relapsers (p= 0.008)
_ Week 24 Evaluation:
HCV RNA negative (<5 IU/mL):
- 10/30 (33%) of prior nonresponders vs.
15/19 (79%) of prior relapsers (p=0.001)
_ Week 48 Evaluation:
HCV RNA negative (<5 IU/mL):
- 9/30 (30%) of prior nonresponders vs.
15/19 (79%) of prior relapsers (p=0.001)
- 2/12 (17%) of African American vs.
22/37 (59%) of non-AA (p = 0.01)
-15/40 (38%) of genotype 1 vs.
9/9 (100%) of non-1 (p = 0.001)
- 16/25 (64%) of weight <85 kg vs.
8/24 (33%) of weight >85 kg (p = 0.03)
_ Logistic regression was used to evaluate the factors predictive of undetectable HCV RNA at week 48. The overall predictive model was statistically significant (chi-square 22.55, p<.0001). Two variables were related to likelihood of undetectable virus: prior response (nonresponder vs. relapser) (OR=0.14, 95% CI 0.03, 0.5) and genotype (1 vs. non-1). The model correctly classified 79.6% of the subjects.
Treatment Discontinuation: in the nonresponder group, 30% discontinued due to side effects, 27% fir viral rebound, and 13% at 24 weeks for nonresponse. In the relapser group, 11% discontinued for side effects, 5% for viral rebound, and 5% for nonresponse at week 24.
Response to Treatment (ITT Analysis) Genotype 1
Week 4
Relapsers: 46%, >2 log decrease
23% undetectable
non-responders: 19% >2 log decrease
4% undetectable
(in both relapser & nonresponder groups a few patients were not tested)
12 weeks
Relapsers: 54% undetectable
39% >2 log decrease
Non-responders: 48% >2 log decrease
13% undetectable
24 Weeks
Relapsers: 69% undetectable
23% >2 log decrease
Non-responders: 30% >2 log decrease
26% undetectable
48 weeks
Relapsers: 69% undetectable
Non-responders: 22% undetectable
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