Prophylaxis with Pegylated Interferon Alfa-2a (Pegasys) plus Ribavirin vs No Pro

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Prophylaxis with Pegylated Interferon Alfa-2a (Pegasys) plus

Ribavirin vs No Prophylaxis after Liver Transplantation

Recurrence of hepatitis C virus (HCV) infection following liver

transplantation continues to be a major problem for many transplant

recipients, sometimes resulting in graft failure and death. In spite

of these potential adverse outcomes, the side effects associated with

use of interferon/ribavirin therapy as prophylaxis or early post-

transplant treatment has limited use of these drugs in this

population.

Researchers conducted a study -- the Phoenix trial -- to compare the

use of prophylaxis with pegylated interferon/ribavirin prior to the

histological recurrence of HCV (prophylaxis arm) versus initiation of

therapy only after histologically apparent recurrence of HCV

(observation arm). Interim results were reported at the 58th Annual

Meeting of the American Association for the Study of Liver Diseases

in Boston (November 2-6, 2007).

Study participants were randomized to one of the 2 arms 10-26 weeks

after orthotopic liver transplantation. Patients in the prophylaxis

arm received 135 mcg pegylated interferon alfa-2a (Pegasys) weekly

for 4 weeks and 180 mcg weekly for 44 weeks, plus 400 mg/day

ribavirin (initial dose), escalating to 1200 mg/day for 48 weeks.

They were then followed for 72 weeks after completing treatment.

The observation arm included patients treated with the same regimen

only upon histological evidence of hepatitis C recurrence

(histological activity index [HAI] score >3 and/or fibrosis score

>2). This group was followed for 24-72 weeks after completing

treatment.

The primary efficacy assessment was the proportion of patients in

each group who experienced histological evidence of hepatitis C

recurrence at 120 weeks after randomization.

Results

• At the time of the report, 55 patients had been randomized to the

prophylaxis arm and 60 to the observation arm.

• In the observation arm, 12 patients (20%) had started therapy due

to meeting the criteria for histological recurrence and had completed

12 weeks of treatment.

• At weeks 4, 12, and 24, respectively, 4 (7.3%), 12 (21.8%), and 21

(38.2%) patients in the prophylaxis arm were HCV negative.

• In the observation arm, the corresponding rates were 0 at week 4

and 4 (33.3%) at week 12.

• Of patients in the prophylaxis and observation arms, 53 (98.1%) and

55 (91.7%), respectively, experienced at least 1 adverse event.

• 23 (42.6%) and 14 (23.3%), respectively, experienced at least 1

serious adverse event.

• ACR was experienced by 2 of 54 (3.7%) patients in the prophylaxis

arm and 3 of 48 (6.3%) untreated patients in the observation arm.

• Significant infections occurred in 4 of 54 (7.4%) and 1 of 48

(2.1%), respectively.

• Clinically significant depression was not observed in either arm.

• Although anemia (16.7% vs 2.1%) and grade 3/4 neutropenia (16.7% vs

8.3%) were more common in the prophylaxis arm than in untreated

patients in the observation arm, these adverse events were likely

related to treatment.

• After 24 weeks of treatment, 38.2% of patients in the prophylaxis

arm were HCV RNA negative.

Conclusion

Based on these findings, the researchers concluded that although

adverse events were common during prophylaxis for post-transplant HCV

recurrence, " the incidence of clinically significant ACR was not

increased by prophylaxis. "

" These findings suggest that peginterferon alfa-2a/ribavirin

prophylaxis is relatively safe and effective in orthotopic liver

transplant recipients, " they noted.

Mayo Clinic College of Medicine, Rochester, MN, USA. California

Pacific Medical Center, San Francisco, CA, USA; Roche Laboratories ,

Nutley, NJ, USA; University of Florida, Gainesville, FL, USA.

11/27/07