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Maintenance Therapy: we don't know if it provides benefit
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I spoke with the study author after his talk. Dr Bruix said the study was too small to draw strong conclusions. There was less varicies that developed in patients receiving treatment presumably but not proven as there were no biopsies that fibrosis may have been provided. But a different study would need to be performed to establish maintenance therapy is beneficial. He said based on what we know now he would not recommend maintenance therapy yet, because it has side effects. He also said i response to my comment as the microphone as several pthers said in talking with me that HALT-C was designed 10 years ago and we have learned more since then so today we would design a different study. So the results reported by HALT-C investigators is clearly not as firm as they said but perhaps we have not developed a good understanding of whether maintenance therapy can provide benefit and slow or prevent fibrosis progression, but I guess I can say the firm statement from HALT-C investigators that maintenance therapy does not slow or stop fibrosis or provide some benefit appears not to be true, today you can say we don't know if it provides benefit. Studies subsequent to HALT-C suggest perhaps therapy does provide benefit but we don't know for sure.
PEGINTRON MAINTENANCE THERAPY IN CIRRHOTIC (METAVIR F4) HCV PATIENTS, WHO FAILED TO RESPOND TO INTERFERON/RIBAVIRN (IR) THERAPY: FINAL RESULTS OF THE EPIC3 CIRRHOSIS MAINTENANCE TRIAL
J. Bruix1, T. Poynard2, M. Colombo3, E. Schiff4, J. Reichen5, K. Burak6, E.J.L. Heathcote7, T. Berg8, J.-L. Poo-Ramirez9, C. Brandao Mello10, R. Guenther11, C. Niederau12, R. Terg13, N. Bopari14, J. Harvey14, L.H. Griffel14, M. Burroughs14, C.A. Brass14, J.K. Albrecht14
1Hospital Clinic I Provincial, Barcelona, Spain, 2Hopital La Petie Salpetriere, Paris, France, 3Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy, 4University of Miami, Miami, FL, USA, 5Universitaet Bern, Bern, Switzerland, 6Heritage Medical Research Clinic - University of Calgary, Calgary, AB, 7University Health Network - Toronto Western Hospital, Toronto, ON, Canada, 8Charite - Campus Virchow Klinikum, Berlin, Germany,9CIF BIOTEC/Hospital Medica Sur, Mexico City, Mexico, 10Hospital Universitario Gaffree & Guinle, Rio de Janeiro, Brazil, 11Universitaetsklinikum Schleswig-Holstein, Kiel, 12St. Josef-Hospital Oberhausen, Oberhausen, Germany,13Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo, Buenos Aires, Argentina, 14Schering-Plough Research Institute, Kenilworth, NJ, USA
Background and aims: EPIC3 includes a prospective trial designed to assess the efficacy and safety of long-term low-dose maintenance with PegIntron 0.5 mcg/kg/week in subjects who previously failed treatment with any alfa-interferon plus ribavirin.
Methods: 631 subjects (626 modified ITT) were randomized to PegIntron or observational control. 454 subjects were from the EPIC3 retreatment study, and 172 were direct enrollers into this study. The primary efficacy measure for the study was time to development of first clinical event defined as
1) liver decompensation:
a. variceal bleeding,
b. Child-Pugh class C, c. ≥grade 2 hepatic encephalopathy, d. ascites requiring therapeutic paracentesis and/or additional therapy;
2) development of HCC;
3) death;
4) liver transplantation.
All events except death and transplantation were adjudicated by an independent committee of experts blinded to the study arm. Secondary efficacy analyses included time to disease progression including additional events of Child-Pugh class B, emergence of varices, and enlargement of pre-existing varices requiring additional therapy.
Results: 36 subjects in the control arm and 27 subjects in the treatment arm had clinical events [P=0.14, HR 1.45, 95% CI 0.88-2.40]. On secondary analysis there were 87 clinical events in the control arm and 63 in the treatment arm [P=0.01, HR 1.56, 95% CI 1.13-2.17]. The main events causing the difference on secondary analysis were emergence or enlargement of varices (43 control, 16 treatment). In subjects with baseline esophageal varices (n=82) there were 14 events in the observation arm and only 4 in the treatment arm (P=0.01). Overall the safety profile for PegIntron was similar to that in previous studies; however, there were more infectious serious adverse events in the treatment group (25 vs 3). None were unexpected events, nor was there a pattern to them
Conclusions: In the primary analysis PegIntron maintenance was not superior to observational control in preventing the occurrence of clinical events. However, 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.
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