Pegylated
Interferon Alfa-2a (Pegasys) plus
Ribavirin in Non-responders to Pegylated
Interferon Alfa-2b (PegIntron) plus
Ribavirin: Final Results of the REPEAT
Trial Individuals
with chronic hepatitis C who do not respond
to initial treatment with pegylated
interferon plus ribavirin (non-responders) have few options for successful
subsequent therapy. Two alternatives available to these non-responders are to
receive intensified treatment with higher fixed-dose induction of pegylated interferon
and/or longer treatment duration in the hope that they will achieve sustained
virological response (SVR).
In the REPEAT study, researchers compared the
outcomes of these 2 strategies in 932 patients who were nonresponders to at least
12 weeks of treatment with pegylated
interferon alfa-2b (PegIntron) plus ribavirin. Final results were presented
at the 58th Annual Meeting of the American Association for the Study of Liver
Diseases (AASLD 2007) in Boston (November 2-6, 2007).
Eligible patients
were randomized (2:1:1:2) to 1 of 4 regimens:
Arms A and B: pegylated
interferon alfa-2a (Pegasys) 360 mcg/week for 12 weeks, then 180 mcg/week for
a further 60 or 36 wks, respectively;
Arms C and D: pegylated interferon
alfa-2a 180 mcg/week for 72 or 48 weeks, respectively.
All patients also
received 1000-1200 mg/day weight-based ribavirin.
The primary endpoint
was SVR, or undetectable HCV RNA (< 50 IU/mL) 24 weeks after completion of
therapy.
Results •
A total
of 942 patients were randomized and began dosing.
•
Key
baseline characteristics were similar across study arms.
•
The
primary endpoint was met: SVR was significantly higher for Arm A (16%) compared
with Arm D (9%).
•
A
pooled analysis of the 72-week arms versus the 48-week arms showed that 72 weeks
of treatment had the greatest impact on treatment success, with a doubling of
the SVR rate compared to 48 weeks (16% vs 8%).
•
A
pooled analysis of the induction-dose arms versus standard-dose arms showed that
treatment with higher fixed-dose induction for this difficult-to-treat patient
population did not provide significant additional benefit.
•
Response
at week 12 was a strong predictor of successful treatment.
•
Of
patients whose HCV RNA was undetectable after 12 weeks of therapy, 57% in the
72-week arms went on to achieve SVR, compared with only 4% of those who still
had detectable virus at 12 weeks.
In
conclusion, the authors wrote, "In these difficult to cure patients with
prior documented non-response to pegylated interferon alfa-2b/ribavirin, re-treatment
with fixed-dose induction and longer duration with pegylated interferon alfa-2a
(Pegasys)/ribavirin provided the highest SVR rates and the lowest relapse rates."
"Re-treatment
with 72 weeks of pegylated interferon alfa-2a provided higher SVR rates than 48
weeks, irrespective of induction." Results
of REPEAT Study
|
|
Pegylated interferon
alfa-2a (Pegasys)
plus ribavirin
1000-1200 mg/day |
| |
A (n=317)
360/180 mcg/week
(72 week)
|
B (n=156)
360/180 mcg/week
(48 week) |
C (n=156)
180 mcg/week
(72 week) |
D (n=313)
180 mcg/week
(48 week) |
|
Males (%) |
64% |
60% |
69% |
68% |
|
Mean ± SD Age
(years) |
48.1 ± 8.7 |
48.8 ± 9.9 |
49.4 ± 8.5 |
48.5 ± 9.0 |
|
Caucasian (%)
|
88% |
90% |
88% |
90% |
|
Mean ± SD Weight
(kg) |
81.5 ± 18.2 |
81.1 ± 16.8 |
81.2 ± 16.0 |
80.9 ± 16.9 |
|
Genotype 1 (%)
|
91% |
91% |
91% |
91% |
|
Mean ± SD baseline
HCV RNA (x 106 IU/mL) |
5.4 ± 6.4 |
5.3 ± 7.1 |
4.9 ± 5.1 |
4.9 ± 6.0 |
|
Cirrhosis (%)
|
25% |
29% |
30% |
28% |
|
End-of-treatment
response rate, n (%) |
99 (31%) |
52 (33%) |
48 (31%) |
88 (28%) |
|
SVR rate, n/N (%)
Overall
baseline viral load ≤800 000
baseline viral load
>800 000 |
52/317 (16%)
22/61
(36%)
29/244 (12%)
|
11/156 (7%)
2/22
(9%)
9/130 (7%)
|
22/156 14%)
5/25
(20%)
17/128 (13%)
|
27/313 (9%)
9/62
(15%)
16/233 (7%)
|
| Relapse Rate,
n/N* (%) |
48/92 (52%) |
38/49 (78%) |
30/47 (64%) |
55/81 (68%) |
|
Premature d/c
for safety, n (%) |
37 (12%) |
7 (4%) |
18 (12%) |
20 (6%) |
|
Patients with Serious adverse events, n (%)
Overall
Hematological |
33 (10%)
5 (2%)
|
14 (9%)
-
|
28 (18%)
3 (2%)
|
33 (11%)
6 (2%)
|
| Pegasys dose modifications, n (%) |
72 (23%) |
41 (26%) |
36 (23%) |
57 (18%) |
*N=Patients
with negative end-of-treatment (EoT) HCV RNA and · 1 post-EoT HCV RNA value 11/06/07
Reference
DM Jensen, B Freilich, P Andreone, and others. Pegylated
interferon alfa-2a (40KD) plus ribavirin (RBV) in prior non-responders to pegylated
interferon alfa-2b (12KD)/RBV: final efficacy and safety outcomes of the REPEAT
study. 58th Annual Meeting of the American Association for the Study of Liver
Diseases. Boston, MA. November 2-6, 2007. Abstract LB 4. Following
are excerpts from Roche's press announcement about the REPEAT study results: Treatment
with Pegasys/Copegus Provides Hope for Hepatitis C Patients Whose Infection Did
Not Initially Respond to Peg-Intron/Ribavirin (Boston
- November 2, 2007) - Roche today announced final results from the REPEAT study,
which demonstrated that treatment with once-weekly Pegasys (peginterferon alfa-2a)
and daily Copegus (ribavirin) for 72 weeks is a promising treatment option for
patients whose infection did not respond to previous treatment with another pegylated
interferon (PegIntron, peginterferon alfa-2b) and ribavirin. Further,
the results showed that response at 12 weeks was a powerful predictor of the eventual
outcome: the majority of patients with undetectable virus at 12 weeks went on
to achieve a sustained virological response (SVR) after 72 weeks of treatment,
while few patients with detectable virus at 12 weeks achieved SVR. These data
were presented in an oral session at the 58th Annual Meeting of the American Association
for the Study of Liver Diseases (AASLD 2007), being held in Boston, Nov. 2-6. "One
of the greatest areas of need in hepatitis C today is to find solutions for patients
who have not seen treatment success with an initial course of therapy. REPEAT
is an important study which adds significantly to our knowledge about how to manage
these patients, demonstrating that extending treatment with Pegasys and Copegus
is a promising option," said Donald Jensen, M.D., Professor of Medicine and
Director of the Center for Liver Diseases at the University of Chicago Hospital
in Chicago, and lead investigator in REPEAT. "A
significant finding from REPEAT is confirmation of the reliability of using a
patient's response at 12 weeks as a predictor of treatment success, even in patients
with cirrhosis. This means that patients who achieve undetectable virus at 12
weeks can continue treatment with a good likelihood of success. It also means
that clinicians can confidently discontinue treatment in patients who do not achieve
an early response." Source
Roche Laboratories. Treatment with Pegasys/Copegus Provides Hope for
Hepatitis C Patients Whose Infection Did Not Initially Respond to Peg-Intron/Ribavirin.
Press Release. November 2, 2007.
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