Treatment with Pegasys of Non Responders to PEG-Intron: Preliminary 24-week Results

The combination therapy of peginterferon (PEG-IFN) and ribavirin (RBV) is the standard of care for patients with hepatitis C infection. Preliminary data from the HALT-C trial indicates efficacy of PEG-IFN alfa-2a (Pegasys) + ribavirin (RBV) in achieving sustained virologic responses (SVR) in patients with prior treatment.

There is no available literature that examines the efficacy of PEG-IFN alfa-2a in patients that were prior non-responders to PEG-IFN alfa-2b (PEG-Intron).

In the past 18 months at Johns Hopkins medical center, 55 consecutive patients (M=28/F=25; age 21-61 years) with HCV infection were treated with PEG-IFN alfa-2a 180mcg QW and RBV 1000mg (<75kg) or 1200 mg (>75 mg) PO QD x 48 weeks.

Patient characteristics were: Genotype 1a/ 1b: 89% (N=49); genotype 2: 3.6% (N=2); genotype 3: 7% (N=4) and genotype 4: 2% (N=1).

There were 15 patients (27%) that were prior non-responders to PEG-IFN alfa-2b/RBV, with detectable HCV RNA on at least 6 months of previous treatment. All 15 patients were genotype 1 with an average viral load of 3,100,000 IU/ml.

In addition, 7 patients were non-responders to prior treatment with standard IFN alfa-2b/RBV, and the rest (N=33) were naive to previous treatment.

Virologic assessment was performed by ultrasensitive assays (Heptimax/Quest Diagnostics <5 IU/mL or Quantasure/Labcorp <5 IU/mL).

Results

Overall virologic response rate at 24 weeks on therapy was observed in 17/33 (51%) naive patient, 3/7(43%) non-responders to standard IFN/RBV and 6/15 (40%) non-responders to PEG-IFN alfa-2b /RBV.

Of the PEG-IFN alfa-2b/RBV non-responders (N=15) that failed re-treatment with PEG-IFN alfa-2a/RBV, 33% (3/9) were African American (AA), 55% (5/9) were male, 77% (7/9) and had a null response (NR) (<1 log drop) to prior treatment.

In comparison, PEG-IFN alfa-2b/RBV non-responders that subsequently responded to PEG-IFN alfa-2a/RBV, only 16% (1/6) were AA, 50% (3/6) were male, 67% (4/6) had NR to prior treatment. All 9 patients were genotype 1 and had comparable viral loads (p=NS).

Conclusion

In conclusion, the authors write, “Preliminary 24-week virologic assays using ultrasensitive HCV RNA assays suggests significant differences in viral kinetic responses to subsequent treatment with PEG-IFN alfa-2a/RBV.”

“Further studies are ongoing to determine SVR, but a 40% efficacy in achieving undetectable HCV RNA level at 24 week appears promising in providing further treatment options for a select group of patients.”

[Editor’s Note: These are preliminary results in a small number of patients.]

05/19/04

Reference
N Zeng and others. Treatment of HCV Infected Patients, Including Non-Responders to PEG-IFN alfa-2b/RBV, with PEG-IFN alfa-2a/RBV: The Johns Hopkins Experience. Abstract 1233 (poster). Digestive Disease Week. May 15-20, 2004. New Orleans, LA.