Switching from Peginterferon Alfa-2b (Peg-Intron) for Recurrent HCV to an Escalating Peginterferon Alfa-2a (Pegasys) Regimen May Improve Tolerability Post Liver Transplantation

Recurrence of hepatitis C post orthotopic liver transplantation (OLT) is universal. Response rates to interferon and ribavirin are suboptimal, with appreciable side effects leading to discontinuation in 30%.

In this study, a standardized protocol of pegylated interferon α-2b (Peg-Intron) and ribavirin therapy was implemented in January 2001 to treat patients with histological recurrent hepatitis C virus post OLT.

Patients were commenced on pegylated interferon alfa 2b and ribavirin at doses of 1.5 million units/week and ribavirin 11mg/kg. Patients who did not respond or were unable to tolerate therapy were switched to an escalating regimen of pegylated interferon α-2a (Pegasys) commenced at 90mcg/week, titrating up to 180 mcg/week over 3 months and ribavirin at 7mg/kg up to 11mg/kg over 3 months.

Hematopoietic growth factors were used for Hb < 12.0g/dL and for total WBC

< 1.5 x 103 u/L. Response to therapy was assessed as on treatment virological response (OTR) and side effects were recorded in a retrospective chart review.

Results

Twenty-seven patients underwent treatment for recurrent HCV with the above protocol. The majority of patients (80%) were genotype 1.

Ten (37%) patients discontinued therapy early (< 6 months) due to side effects. Eight (30%) had significant weight loss (>5kg). Twenty-two (81%) developed anemia and 10 were treated with erythropoietin, 9 (33%) developed neutropenia and 8 were treated with G-CSF. Seven patients (26%) required antidepressant therapy. Eight (30%) achieved OTR following 1 year of therapy.

Ten (37%) patients were switched to an escalating pegylated interferon α-2a and ribavirin regimen due to lack of OTR in 2, constitutional side effects in 5, arthritis in 1 and symptomatic anemia and neutropenia unresponsive to growth factor support in 2.

These patients had been on therapy for a mean of 6.2 months (range 2 - 13) prior to switching and only 1 had achieved OTR.

After switching to pegylated interferon α-2a, 3 additional patients (33%) achieved OTR and no patients discontinued therapy after a mean of 5.5 months on therapy.

Conclusions

The authors conclude, “Our initial data suggest that an escalating peg-interferon α-2a combination regimen may be tolerated better than combination peg-interferon α-2b in some patients post OLT and thus allow better OTR.”

“Those problematic patients who do not tolerate combination therapy post OLT may tolerate therapy better using an escalating combination regimen with aggressive growth factor support.”

06/04/04

Reference
N Kontorinis and others. Switching from Peg-Interferon α-2b to an Escalating Peg-Interferon α-2a Regimen for Recurrent Hepatitis C Post Liver Transplantation May Improve Virological Response and Tolerability. Abstract 1177 (poster). Digestive Disease Week. May 15-20, 2004. New Orleans, LA.