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Pegasys/RBV Prophylaxisly Administered After Liver Transplant
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Reported by Jules Levin
AASLD, Oct 27-31, 2006, Boston, MA
"A Randomized Controlled Trial of Prophylactically Administered Peginterferon Alfa-2a Plus Ribavirin vs No Prophylaxis Following Orthotopic Liver Transplantation (OLT) for Hepatitis C: A Report of Initial
Safety and Tolerability"
Natalie H. Bzowej MD, PhD, California Pacific Medical Center; David Nelson, MD, University of Florida College of Medicine; James A. Thommes, MD, Roche Laboratories; Fayez M. Hamzeh, MD, PhD, Roche Laboratories; and Michael Charlton, MD, Mayo Clinic College of Medicine
Introduction
Recurrent HCV infection following OLT is a substantial source of morbidity, mortality, and graft loss1-3
Minimal data are available concerning the timing, efficacy and safety of antiviral therapy for the amelioration of the posttransplant recurrence of hepatitis C infection.
1. Gane EJ, et al. N Engl J Med. 1996;334:815-20; 2. Feray C, et al. Hepatology. 1994;20:1137-43; 3.Charlton M, et al. Hepatology. 1998;28:823-30.
AUTHOR CONCLUSIONS
AEs observed during prophylaxis with peginterferon alfa-2a and ribavirin for post-OLT HCV recurrence were similar to those previously reported1
(1. Fried MW, et al. N Engl J Med. 2002;347:75-982.)
AEs occurred in 94% of patients, with 19% experiencing serious AEs necessitating treatment withdrawal
During the first 12 weeks, no signs of ACR occurred in either study arm
These preliminary findings suggest that prophylaxis with peginterferon alfa-2a plus ribavirin is relatively safe and well-tolerated in OLT recipients
PATIENTS & METHODS
The PHOENIX study was designed to test the effectiveness of prophylaxis with peginterferon alfa-2a plus ribavirin
-- Prophylaxis arm: Treatment before histological recurrence of HCV
-- Observation arm: Treatment only upon histological recurrence of HCV (HAI ≥3 and/or FS ≥2 by Batts-Ludwig scoring system)
Patients were randomized 10 to 26 wks after OLT
Treatment regimen:
-- 135 _g/wk peginterferon alfa-2a for 4 wks; then 180 _g/wk for 44 wks
-- 400 mg/d ribavirin (initial dose), escalating over 12 weeks to 1200 mg/d, for 36 wks
To date, 115 patients have been enrolled
We show preliminary safety and tolerability data during the first 12 weeks in the first 60 randomized patients
Study Schema: Prophylaxis Arm
Pegasys/RBV prophylaxis treatment for 48 wks started 10-26 wks post-LT.. Biopsy performed 48 & 120 wks post-randomization.
Key Inclusion Criteria
HCV identified by PCR or bDNA pretransplantation
-- No biochemical or histological inclusion criteria
Adult primary, whole single organ recipient (deceased donor) within ≥10 and ≦26 weeks
Negative urine pregnancy test within 24h of treatment initiation
Standard ribavirin contraception requirements
Patients with a pre-LT diagnosis of hepatocellular carcinoma (HCC) may be enrolled provided:
-- No evidence of extrahepatic spread, tumor is solitary and <5cm in diameter or there are no more than three separate tumor sites, each <3 cm in diameter
Results Patient Disposition
33 randomized to prophylaxis treatment. 32 recd 1 or more doses of study meds. 7 withdrew. 25 remain on treatment. 27 went to observation arm. 20 remain without treatment, 4 remain on treatment.
Treatment Withdrawals
Of the 32 patients in the prophylaxis arm, 6 (19%) have withdrawn from study medications for AEs
5 have withdrawn from both peginterferon alfa-2a and ribavirin
-- 1 from peginterferon alfa-2a due to rash and from ribavirin due
to anemia
-- 1 due to thrombocytopenia
-- 1 due to increased bilirubin
-- 1 due to dehydration
-- 1 due to neutropenia
1 has withdrawn from ribavirin only due to anemia
None of the 4 treated patients in the observation arm has withdrawn
No clinically apparent episodes of ACR occurred through week 12
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