A Pilot Study of Combination Treatment with Consensus Interferon (Infergen) and Interferon Gamma 1b (Actimmune) in Nonresponders to Peginterferon Plus Ribavirin
Treatment of chronic hepatitis C with peginterferon alfa (Peg IFN alfa) and ribavirin leads to a sustained virologic response in approximately 50% of patients. Response to therapy can be predicted early in the course of treatment (week 12) by assessment of serum HCV RNA.

Patients who have not had at least a 2 log10 reduction in serum HCV RNA by week 12 have a 97-100% chance of not responding to therapy and typically therapy is stopped. These patients have been termed “Null Responders”.

Preclinical studies have demonstrated strong synergistic antiviral and immunomodulatory effects of the combination of IFN alfacon 1 (consensus interferon; Infergen) and IFN-gamma 1b (Actimmune) in preclinical models of HCV.

Given these data, the researchers conducted a retrospective analysis of 50 Null Responders to pegylated IFN alfa 2a + ribavirin therapy who were retreated with IFN alfacon 1, 15 mcg SQ daily, and IFN-gamma 1b 50 mcg SQ TIW for 48 weeks.

All patients had previously received pegylated interferon alfa 2a (Pegasys) and ribavirin for 12 weeks, and did not have at least a 2- log10 drop in HCV RNA. Serum HCV RNA was assessed at weeks 8, 12 and 24 to determine early virologic response and will be assessed at weeks 48 and 72 to determine end of treatment and sustained virologic responses.

Patients were monitored for constitutional symptoms and bloods were collected for serum chemistries and hematological evaluations.

Results
At the end of 8, 12 and 24 weeks of therapy, 36%, 40% and 46% of these Null-responder patients had undetectable serum HCV RNA respectively (Amplicore qualitative assay, Roche Diagnostics, Indianapolis, In). One patient discontinued therapy because of constitutional symptom complaints while all other patients tolerated the therapy well.

By week 24, eleven patients (22%) required filgrastim for reductions in absolute neutrophils counts to below 0.75 X 10 9 /L. Prior to initiation of therapy with IFN alfacon1 and IFN gamma 1b and following 12 weeks of Peg IFN alfa 2b + ribavirin therapy the mean hemoglobin level was 11.6 +- 0.7. By week 8 all patients recovered Hemoglobin levels to normal with no use of erythopoeitin indicating that the combination of IFN alfacon1 and IFN gamma 1b does not interfere with hemoglobin recovery.

Conclusions
In conclusion, the authors write, “Retreatment of pegylated interferon alfa 2 + ribavirin Null Responders with the combination of IFN alfacon 1 and IFN gamma 1b is well tolerated and preliminary analysis of early virologic response suggests that this treatment may be of potential benefit in these difficult to treat patients.”

“Further analysis will assess SVR and a larger dose finding study of the combination of IFN alfacon1 and IFN gamma 1b has been initiated.”

C l Leevy II and others. INTERIM RESULTS OF A PILOT STUDY OF THE COMBINATION OF TYPE 1 (IFN ALFACON 1) AND TYPE 2 (IFN GAMMA 1B) INTERFERONS IN CHRONIC HEPATITIS C PATIENTS WHO HAVE FAILED TO RESPOND TO PEG-INTERFERON ALFA 2A PLUS RIBAVIRIN. Abstract 530 (poster). 55th AASLD. October 29-November 2, 2004. Boston, MA.