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Pegasys in IFN/RBV Relapsers & Nonresponders Canadian EAP
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Reported by Jules Levin
These study results were reported at both EASL & DDW, April/May 2005.
....19% of previous genotype 1 IFN/RBV non-responders & 31% of previous genotype 1 IFN/RBV relapsers achieved an SVR (sustained viral response) in the Canadian Expanded Access Program.... For genotype 2/3 non-responders 35% achieved SVR, for genotype 2/3 relapsers 51% achieved SVR....Patients received Pegasys plus 800mg/day of ribavirin, suggesting response rates might have been better if the currently recommended regimen of 1000/1200 mg/day of ribavirin were used. (This EAP was initiaited before optimal treatment regimens had been established). The study investigators conclude these results "provide a strong rationale for retreating these patients”.
"Peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS)
in chronic hepatitis C patients who failed previous
interferon-based therapy: results of a multicentre
open-label expanded access programme in Canada”
M. Sherman,1 E. Yoshida,2 M. Deschenes,3 M. Krajden,4 V. Bain,5 K. Peltekian,6 F. Anderson,7 K. Kaita,8 S. Simonyi,9 S. Lee10
1University Health Network, Toronto General Hospital, Toronto, ON; 2Vancouver Hospital Health Sciences Centre, Vancouver, BC; 3Royal Victoria Hospital, Montreal, QC;
4British Columbia Centre for Disease Control, Vancouver, BC; 5University of Alberta, Edmonton, AB; 6QEII – Health Sciences Centre, Hepatology Services, Halifax, NS;
7The Liver and Intestinal Research Centre, Vancouver, BC; 8John Buhler Research Centre, Winnipeg, MB; 9Roche, Canada; 10Heritage Medical Research Clinic, Calgary, AB, Canada
A total of 863 patients were assigned to either 24 (genotype 2/3) or 48 weeks (genotype 1) treatment with Pegasys plus ribavirin 800mg/day.
This was open-label program conducted at 18 centers in Canada. Sustained Viral Response (SVR) was defined as <50 IU/mLHCV RNA qualitative PCR, Cobas Amplicor v. 2.0) following 24 week untreated followup period after treatment ended. All patients who received >=1 dose of study drug were included (ITT analysis).
Where documented, most previously treated patients 253/355; 71% had received combination therapy with IFN/RBV:
ITT population: (119 relapsers and 236 non-responders).
(67% of relapsers and 73% of non-responders).
BASELINE CHARACTERISTICS
--42% of patients had cirrhosis (139/33), F3/F4 in genotype 1 group; and 27% (35/93) in genotype 2/3 group.
--50-60% of patients had >500,000 IU/mL HCV RNA (viral load)
--Among genotype 1, 28% had >800,000 IU/mL. Among genotype 2/3 receiving 24 week therapy 34-42% had >800,000 IU/ml.
--BMI (kg/m2) was 26.7-28.
--57-70% were men; among 48 week treatment group (83% genotype 1): 65-70% were men. Among 24 week treatment group 98-100% were genotype 2/3 & 57-66% were men.
RESULTS
Although not mentioned directly in the posters, it appears as though growth factors (EPO for anemia) was not used for patients.
SVR TREATMENT NAÏVE PATIENTS:
55% overall
72% - genotype 2/3
39% - genotype 1
Cirrhotics: 41%
Non-cirrhotics: 50%
These responses were similar to those seen in randomized large phase III studies.
The study investigators concluded the SVR rates immediately below for non-responders & relapsers "provide a strong rationale for retreating these patients”.
SVR FOR NON-RESPONDERS & RELAPSERS:
NON-RESPONDERS
Genotype 1: 20%
Genotype 2/.3: 35%
RELAPSERS
Genotype 1: 35%
Genotype 2/3: 51%
SVR RATE for PREVIOUS NON-RESPONDERS to IFN+RBV:
Genotype 1: 19% (29/149)
Genotype 2/3: 35% (7/20)
RELAPSERS:
G1: 31% (17/54)
G2/3: 52% (12/12)
Table 2. Efficacy pf Pegasys plus ribavirin 800mg/day in relapsers & non responders according to HCV genotype
SAFETY
Similar proportions of relapsers and responders receiving 48 weeks of therapy required peginterferon alfa-2a (40KD) dose modifications for neutropenia (23% vs 19%) or thrombocytopenia (7% vs 6%) and ribavirin dose modifications for anaemia (10% vs 8%) (Table 3).
The overall incidence of serious adverse events was similar in non-responders and relapsers. A total of 12 adverse events were reported in 11 of the 236 non-responders (5%) and a total of 14 adverse events were reported in 9 of 119 relapsers (8%). Overall, 10 events occurring in 9 patients were judged to be related to study treatment by the investigators.
6-12% of patients experienced anemia (<10 g/dL).
12-25% of patients experienced neutropenia grade 3 or 4.
3-8% of patients experienced thrombocytopenia (reduced platelet counts) grade 3.
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