Saturday Poster Sessions,
HCV Treatment
Topic: Treatment - Pegasys
233. An Open
Label, Comparative, Multicenter Study Of
Peginterferon Alfa-2a Plus Ribavirin in The Treatment Of Patients With Chronic
Hepatitis C/Hepatitis B Co-Infection Versus Those With Chronic Hepatitis C
Monoinfection C. Liu; W. Chuang; C. M. Lee; S. S. Wu;
L. Y. Liao; H. T. Kuo; Y. C. Chao; C. L. Chen; P. J. Chen; D. S. Chen
Introduction:
Pilot studies using conventional interferon plus ribavirin (RBV)
for 6 months to treat patients with dual chronic hepatitis C and B infection
suggested that sustained hepatitis C virus (HCV) clearance rate comparable to
that observed in HCV monoinfected patients could be achieved. We have conducted
a multicenter clinical trial in mono and co-infected patients using
peginterferon-based combination therapy in
Methods:
Eligible patients with active HCV (serum ALT level >=1.5 X
ULN and HCV RNA ≥100,000 copies/mL), with (n=161) or without (n=160)
detectable HBsAg, were enrolled. Patients infected with HCV genotype 1 received
48 weeks of peginterferon alfa-2a 180 μg weekly plus 1000–1200 mg RBV
daily. HCV genotype non-1 patients received 24 weeks of peginterferon alfa-2a
180 μg weekly plus 800 mg RBV daily. The primary efficacy endpoint was
sustained HCV RNA clearance 24 weeks post-treatment (SVR) determined using an
in-house real-time PCR assay (lower limit of detection ~100–1,000 copies/mL).
Secondary efficacy parameters included HBV DNA response (<1,000 copies/mL)
and normalization of serum ALT at end of treatment and 24 weeks post-treatment.
Interim analyses are based on 275 patients (86%) who have completed treatment
and follow-up.
Results:
Patients were recruited from June 2004. The treatment and follow-up was completed in
August 2007 and reported in September 2007.
The majority of dually infected patients were male; The
group containing HCV genotype non-1 mono-infected patients had a higher
proportion of female
patients enrolled than the other patient
groups.
The ITT analysis included all patients that received at least
one dose of study treatment; withdrawn cases with missing data at 24 weeks
post-treatment were counted as treatment failure. A total of 26 (8.1%) patients were withdrawn
prematurely from the study
HCV response
HCV genotype non-1 infected patients had a slightly better
sustained response than genotype 1 patients in both HCV and HBV dually infected
and HCV mono-infected patients. HCV
clearance rates were comparable at the end of treatment (88% vs 94%) and 24
weeks posttreatment (86% vs 88%) for dually infected and HCV mono-infected
patients with non-1 genotype infection, respectively. The majority of HCV genotype 1 infected
patients with dual HCV/HBV infection achieved a sustained response (73%) after
24 weeks of treatment-free follow up and an even higher rate of HCV clearance
was achieved in HCV mono-infected patients (77%). A per protocol analysis, including data for all
patients completing 12 weeks of treatment, shows comparable end-of-treatment
and sustained responses.
HBV response
Virological
·
Of
the 145 dually infected patients with available data for analysis, 68 (46.9%)
had detectable serum HBV DNA pre-treatment
·
Of
the 68 patients with baseline detectable serum HBV DNA, HBV virologic response
(VR) was obtained in 47 (69.1%) at the end of treatment and in 38 (55.9%) at
the end of follow-up
·
Of
the 77 patients with baseline undetectable serum HBV DNA, rebound of HBV DNA
was found in 28 (36.4%), including 16 (20.8%) and 17 (22.1%) at the end of
treatment and follow-up, respectively
·
None
of the HBV rebounds was associated with an elevation of serum ALT >200 IU/L,
and almost all showed an HCV SVR
HBsAg clearance
·
10%
of the dually infected patients cleared HBsAg at the end of treatment-free
follow-up
Summary:
·
A
sustained HCV clearance rate of 73% was achieved at 24 weeks post-treatment in
the most difficult-to-treat patients dually infected with HCV genotype 1 and
HBV
·
In
HCV genotype non-1 dually infected patients, HCV clearance (86%) was achieved
to an extent comparable to that observed in HCV mono-infected patients (77% and
88% for genotype 1 and non-1 infected patients, respectively)
·
In
general there was little difference between HCV response rates between genotype
1 and non-1 infected patients at end of treatment and 24 weeks post-treatment
·
HBV
virologic response was obtained in 56% of the patients with dual HCV/HBV
infection
·
Importantly,
HBsAg clearance was observed in 10% of the dually infected patients
·
36%
of the dually infected patients whose serum HBV DNA were undetectable
pre-treatment experienced rebound of HBV DNA
Conclusion:
Combination therapy of PEGASYS and COPEGUS appears to be safe
and effective for treatment of patients dually infected with HCV and HBV.
Importantly, a substantial proportion of the dually infected patients
achieved HBsAg clearance – an important
indicator of long-term treatment success.
Topic: Treatment - Pegasys
A. Andriulli; C. Cursaro; R. Cozzolongo; A.
Iacobellis; M. R. Valvano; A. Mangia; N. Minerva; D. Bacca; M. Stanzione; A.
Scuteri; G. Montalto; P. Andreone
Background & Aims:
Half of patients with HCV-2 and HCV-3 infection attained
sustained virologic response (SVR) following Peg-interferon alfa-2a (Peg-IFN)
monotherapy. However, guidelines recommend Peg-IFN with ribavirin for 24 weeks
in all patients. Efforts to select patients who might benefit from Peg-IFN
monotherapy have not been pursued.
Methods.
In a multicenter trial, 144 HCV-2 and HCV-3 patients were
started on Peg-IFN alfa-2a (180 μg/wk) and ribavirin (1000-1200 mg/day)
for 12 weeks: those with RVR at week 4 were randomized to either
discontinue ribavirin and remain on Peg-IFN alfa-2a, (n=59) or to
continue combination therapy (n=61). To delineate patients’ features that might
help identify individuals likely to benefit from ribavirin discontinuation, an
SVR prediction model was developed including gender, age, HCV genotype,
baseline HCV-RNA levels, BMI, ALT values, and advanced fibrosis. Stepwise
logistic regression analysis was used to compare P values and odds ratios for
the effect of prognostic factors on either SVR and RVR
rates.
Results:
In the 24 patients with no RVR, 15 (63%) were
end-of-treatment (EOT) responders, and 12 (50%) were SVR. Baseline features of
RVR patients randomized to ribavirin withdrawn or to standard treatment were
not different. All but one RVR patients had EOT response. As expected, SVR
rates were lower after discontinuation of ribavirin: 54% versus 82%
(p<0.001). Twenty-seven (46%) and 10 (17%) EOT patients, respectively,
relapsed during the follow up (difference, 29%, CI 27.5–30.6; p<0.001). In
the discontinuation group, low body weight (p=0.022), low BMI (p=0.034), low
viremia (p<0.01) genotype 3 (p=0.031) and mild liver disease (p<0.01)
were associated with SVR; in the multivariate analysis, low viremia and mild
liver disease remained significant predictors with respective odds ratios of
56.8 (C.I.4.3-745) and 27.3 (CI 1.4-521). In patients who did or did not
discontinue ribavirin, SVR rates were similar in those with < 300,000 IU/ml
viremia (86% vs. 81%) and in patients with intermediate viremia (70% vs. 71%),
but disappointingly low in those with >700,000 IU/ml viremia (37% vs. 88%,
p=0.004).
Conclusions:
·
In
HCV-2 and HCV-3 patients, withdrawn of ribavirin and continuation with Peg-IFN
alfa-2a monotherapy may be appropriate to attain SVR, providing viremia is
cleared early during therapy and associated with low baseline viral load.
·
Our
investigation warrants future prospective testing, since it can give rise to considerable
saving in cost and quality of life related to over-treatment
Topic: Treatment - Pegasys
M. von Wagner; W. Hofmann; G. Teuber; T. Berg; T.
Goeser; U. Spengler; H. Hinrichsen; H. Weidenbach; G. G. Gerken; M. P. Manns;
P. Buggisch; S. Zeuzem
Background:
The impact of amantadine on virologic response of
interferon-based treatment of chronic hepatitis C is controversial.
Dose-dependent increase in HCV RNA decline was observed for amantadine during
first weeks of interferon-based treatment.
Objectives:
Assessment of virologic response rates in patients with
chronic HCV 1-infection treated with 400mg amantadine or placebo in combination
with Peginterferon alfa-2a (40kD) and ribavirin for 48 weeks.
Patients and Methods:
Seven hundred and four previously untreated chronically HCV
genotype 1-infected patients (mean age 46 ± 12 yrs.) received
amantadine-sulphate (400 mg/day) (n=352) or placebo (n=352) in combination with
180 µg peginterferon alfa-2a once weekly and ribavirin (1000-1200 mg/day) for
48 weeks. End of treatment and sustained virologic response after a 24-week
follow-up period were assessed by qualitative RT-PCR (Cobas Amplicor HCV,
sensitivity 50 IU/mL).
Results:
Demographic and baseline virologic parameters were similar in
both treatment groups. For 61 patients (9 %) liver cirrhosis or transition to liver cirrhosis were reported. No significant
differences were observed between patients receiving amantadine or placebo
regarding end of treatment and sustained virologic response, respectively.
Intent-to-treat virologic response rates are given in the Table. On-treatment
drop-out rate in the amantadine-group was significantly higher than in the
placebo-group (32% vs. 23%; p=.01). However, adverse events and laboratory
abnormalities were similar between both groups and per-protocol analysis
revealed similar virologic response rates in both treatment groups (52.8% vs.
54.5%).
Conclusion:
In this large placebo-controlled multicenter study,
amantadine even at a dose of 400mg/day did not improve virologic response of
antiviral treatment with peginterferon alfa-2a and ribavirin.
|
Virologic response |
All |
Peg-IFN + Ribavirin Amantadine |
Peg-IFN + Ribavirin Placebo |
|
end of treatment |
487/704 (69.2%) |
231/352 (65.6%) |
256/352 (72.7%) |
|
end of follow-up |
357/704 (50.7%) |
171/352 (48.6%) |
186/352 (52.8%) |
Topic: Treatment – Extrahepatic
Manifestations
D. Saadoun; M. Resche rigon; D. Sene; L. Perard; J. Piette;
P. Cacoub
Background:
Treatment of hepatitis C-related mixed cryoglobulinemia
(HCV-MC) remains difficult and one-third of patients continue to have active
disease while receiving anti-CD20 monoclonal antibody or antiviral therapy.
Objective:
To report the results of a prospective open study using
rituximab combined with Peg-Interferon (IFN)α2b-ribavirin
in HCV-MC vasculitis.
Patients:
Sixteen consecutive HCV-MC patients were treated with rituximab
(intravenously weekly for 4 weeks) combined with Peg-IFNα2b-ribavirin (for
12 months). All patients had severe active disease which was resistant to
previous combination antiviral therapy.
Results:
Fifteen patients (93.7%) showed rapid clinical improvement,
10 of whom (62.5%) were complete responders. Compared with clinical complete
responders, the partial or non responders had a 3.6 times longer duration of
vasculitis prior to therapy and a lower rate of early virologic response.
Complete response was associated with a significant reduction of cryoglobulin,
rheumatoid factor activity and HCV RNA and increased C4. Treatment was well
tolerated with no infectious complications. Flare-up of psoriasis and worsening
of peripheral neuropathy occurred in one patient each. Clinical relapse
occurred in two patients, which was associated with the simultaneous
reappearance of HCV RNA and cryoglobulin and an increase in the number of
peripheral blood B-cells.
Conclusion:
·
Rituximab
combined with Peg-IFNα2b-ribavirin may act synergistically and represents
a safe and effective therapeutic option in severe HCV-MC.
·
This
therapeutic schedule should be considered as induction therapy for HCV-MC
patients.
Topic: Treatment - Pegasys
237. Twice vs
Once Weekly Dosing
of Peginterferon Alfa 2a in Chronic HCV Genotype 1 Infection: Analysis of Early
Viral Kinetics
J. J. Feld; G. A. Lutchman; R. Loomba; A. A. Modi; Y.
Rotman; P. Nagabhyru; M. Ghany; T. Heller; V. Haynes-Williams; T. Liang; A. U.
Neumann; J. H. Hoofnagle
Background:
Treatment outcomes in chronic hepatitis C are highly
correlated with early viral kinetics. Pegylation of interferon greatly improved
treatment responses and allowed for once weekly dosing. However viral kinetic
data have shown that many patients receiving peginterferon weekly have a
rebound in HCV RNA between doses. This may result in suboptimal viral
inhibition and prolong time to clearance of viremia.
Aim:
To compare early viral kinetics
between once and twice weekly dosing of peginterferon in patients with chronic
HCV genotype 1.
Methods:
Consecutive patients with HCV genotype 1 were divided into 2
groups: Group A received peginterferon alfa 2a
180μg once weekly and weight-based ribavirin for 4 weeks and Group B
received an initial 180μg dose of peginterferon followed by 90μg
twice weekly plus ribavirin for 4 weeks. Both groups were then treated with
peginterferon 180μg once weekly and ribavirin for an additional 44 weeks.
HCV RNA was measured at 0, 12, 24, 48 and 72 hrs and at days 7, 9, 14, 21 and
28. Early viral kinetics and baseline characteristics were compared.
Results:
Patients in Group A (n=25) had similar baseline
characteristics to those in Group B (n=25): sex (56% vs 62% male), race (76% vs
80% Caucasian) and HCV RNA level (6.18 vs 6.29 log IU/ml). The groups had
similar first phase (day 0-3) kinetics (Group A -0.76 log vs Group B -0.10
log), but starting at day 3, HCV RNA levels diverged (Figure).
Note: 1 patient in Group B
became HCV negative and were not counted in the
results.
|
|
Group A |
Group B |
P value |
|
PCR( – )at Day 28 |
12 % |
17 % |
0.70 |
|
PCR (+) at week 12 |
61 % |
78 % |
0.37 |
|
EVR |
83 % |
83% |
1.0 |
|
SVR |
56 % |
47 % |
0.75 |
|
Relapse |
26 % |