Interferon alfa-2b (PegIntron) Maintenance Monotherapy May Reduce Esophageal Varices
in Hepatitis C Patients with Cirrhosis
Over years or decades, people with chronic
hepatitis C virus (HCV) infection may develop advanced liver disease, including
cirrhosis and hepatocellular
carcinoma (HCC). In patients with compensated cirrhosis, the liver can still
carry out its vital functions, but as disease progresses they may develop decompensated
cirrhosis, characterized by symptoms including ascites (abdominal fluid accumulation),
hepatic encephalopathy, and bleeding varices (stretched and weakened veins) in
the esophagus and stomach.
interferon-based therapy has been shown to slow, halt, or even reverse liver disease
progression. It remains unclear, however, whether interferon maintenance monotherapy
is beneficial for patients who do not achieve a sustained response to interferon/ribavirin
combination therapy. In the HALT-C
trial, for example, low-dose pegylated
interferon alfa-2a (Pegasys) monotherapy did not reduce the rate of disease
progression or death, though it did appear to improve various markers of liver
At 44th Annual Meeting of the European Association
for the Study of the Liver (EASL 2009) last month in Copenhagen, researchers
presented results from the international EPIC3 study, sponsored by Schering-Plough,
which included a prospective trial designed to assess the efficacy and tolerability
of long-term, low-dose maintenance therapy with pegylated
interferon alfa-2b (PegIntron).
A total of 631 patients who did not
achieve sustained response to combination therapy with conventional or pegylated
interferon alfa plus ribavirin were randomly assigned to receive either 0.5 mcg/kg/week
of pegylated interferon alfa-2b (the usual dose in combination therapy is 1.5
mcg/kg/week) or observation with no further treatment. 454 participants rolled
over from an earlier EPIC3 re-treatment phase, while 172 enrolled directly in
the maintenance phase.
The primary efficacy endpoint was time to development
of a first clinical event, defined as liver decompensation (variceal bleeding,
grade 2 or higher hepatic encephalopathy, ascites requiring treatment, or Child-Pugh
class C), development of hepatocellular carcinoma, liver transplantation, or death.
Secondary endpoints included time to disease progression, Child-Pugh class B events
other than those including in the primary endpoint, emergence of varices, and
enlargement of pre-existing varices requiring additional treatment.
In the primary analysis, 27 patients in the maintenance therapy arm experienced
clinical events, compared with 36 in the untreated control arm, not a statistically
significant difference (hazard ratio [HR] 1.45; P = 0.14).
In the secondary analysis, 63 clinical events occurred in the maintenance therapy
arm compared with 87 in the control arm, which did reach statistical significance
(HR 1.56; P = 0.01).
Development or enlargement of varices accounted for a majority of events making
up the difference between the primary and secondary analyses (16 in the maintenance
arm, 43 in the control arm).
Among 82 participants with esophageal varices at baseline, there were 4 events
in the maintenance therapy arm versus 14 in the control arm, again a significant
difference (P = 0.01).
The overall safety profile of pegylated interferon was similar to that observed
in prior studies.
However, there were significantly more infectious serious adverse events in the
maintenance therapy arm compared with the untreated arm (25 vs 3).
the primary analysis, the investigators concluded, "PegIntron maintenance
was not superior to observational control in preventing the occurrence of clinical
However, they continued, "there was a statistically
significant reduction in clinical events of hepatic decompensation on protocol-defined
secondary analysis as well as in subjects with pre-existing esophageal varices.
These data suggest that PegIntron therapy may delay the progression of portal
hypertension and associated bleeding events."
Hospital Clinic I
Provincial, Barcelona, Spain; Hopital La Petie Salpetriere, Paris, France; Ospedale
Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy; University of
Miami, Miami, FL; Universitaet Bern, Bern, Switzerland; Heritage Medical Research
Clinic, University of Calgary, Canada; University Health Network, Toronto Western
Hospital, Toronto, Ontario, Canada; Charite - Campus Virchow Klinikum, Berlin,
Germany; CIF BIOTEC/Hospital Medica Sur, Mexico City, Mexico; Hospital Universitario
Gaffree & Guinle, Rio de Janeiro, Brazil; Universitaetsklinikum Schleswig-Holstein,
Kiel, Germany; St. Josef-Hospital Oberhausen, Oberhausen, Germany; Hospital Municipal
de Gastroenterologia Dr. Bonorino Udaondo, Buenos Aires, Argentina; Schering-Plough
Research Institute, Kenilworth, NJ.
Bruix, T Poynard T, M Colombo, and others. PegIntron
Maintenance Therapy in Cirrhotic (Metavir F4) HCV Patients Who Failed to Respond
to Interferon/Ribavirin (IR) Therapy: Final Results of the EPIC3 Cirrhosis Maintenance
Trial. 44th Annual Meeting of the European Association for the Study of the
Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009.
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