icon_folder.gif   Conference Reports for NATAP  
  AASLD ( American Association for the Study of Liver Diseases)
November 9-13, 2001, Dallas
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Early week 24 African-Americans Response to Pegasys + Ribavirin
Reported by Jules Levin
  Studies have shown African-Americans respond less well to HCV therapy than Caucasians. Interferon monotherapy achieved a 12% viral response rate for Caucasians and 2% for African-Americans. The lower response rate is at least partly due to the high prevalence of genotype 1 among African-Americans. It is also postulated that there may be an immune genetic basis for this. A large NIH is being prepared now to look at African-American response to HCV therapy. Combination therapy with ribavirin added to interferon improved response rates for Caucasians and African-Americans. And pegylated interferon with ribavirin has improved response to therapy. In a recently reported study, African-Americans had a 15% viral response rate with Pegasys monotherapy compared to 0% for African-Americans receiving standard IFN.
This study looks at the effectiveness and safety of peginteferon alfa-2a (Pegasys) in combination with ribavirin in non-Hispanic African-Americans (AAs) compared to non-Hispanic Caucasians (CA). Preliminary 24 week data is presented here. 74 previously untreated AAs and 28 caucasians with genotype 1 and elevated ALT received Pegasys+1000-1200mg per day of ribavirin (based on body weight (<75 kg or >75 kg). Treatment was for 48 weeks with an additional 24 weeks for followup. Outcome of therapy was assessed as virologic response as defined by HCV-RNA <50 IU/mL (undetectable), and biochemical response (normalization of ALT). Virologic response was also defined as >2 log drop in HCV-RNA. High viral load was defined as HCV-RNA >1 million IU/mL. 3 AA patients were enrolled for every CA enrolled.
Average age of patients was about 45. AAs weighed 91 kg, CA 84 kg. 70% AA men, 60% CA men. AA ALT 62, CA ALT 64. AAs had 58% high viral load, CA had 43% high viral load. About 38% acquired HCV by IVDU.
At baseline, AA patients had higher weight and HCV-RNA than CA patients. And a greater percentage of men were in the AA group.
46 of 74 ongoing AA patients and 19 of 28 ongoing CA patients have completed 24 weeks of treatment. For virologoc response at week 24, 51 AA and 23 CA were included in the analysis. For biochemical response at week 24, 49 AA and 23 CA patients were included in this analysis. Patients receiving at least one dose of study medication who have discontinued prior to 48 weeks of treatment were considered nonresponders from the time of discontinuation. Up to week 24, AA patients exhibited a lower virologic response rate compared with CA patients.
HCV-RNA >2-log drop   AA   CA
Week 24   57%   74%
HCV-RNA <50 IU/mL (undetectable)   AA   CA
Week 24   49%   65%
Normalization of ALT   AA   CA
Week 24   59%   47%
89% of AAs and 100% of CA had at least one adverse event.
Most Frequent Adverse Events   AA   CA
Headache   43%   64%
Fatigue   39%   50%
Rigors   28%   32%
Nausea   15%   43%
Myalgia (aches)   19%   29%
  No unexpected side effects related to the study medications have been noted. Nine serious adverse events have been reported, including the following: fibroid uterus, acute allergic response, acute abdomen, shortness of breath, chest pain, thrombocytopenia (reduced platelets), cellucitis, small intestinal obstruction, and dehydration. Three serious adverse events were reported due to treatment: thrombocytopenia, acute allergic reaction, and chest pain). One serious adverse event (thrombocytopenia) resulted in premature discontinuation. At the time of thios analysis 5 AA and 2 CA patients have discontinued therapy: 2 AA and 2 CA due to expected adverse events/intercurrent illness; 1 AA and 2 CA due to refusal of treatment; 1 AA due to failure to return; and 1 AA due to abnormality of lab test.
These are early and preliminary test results. 48 week results will be more reliable. It,s also important to remember that a viral response is not the only goal of therapy. IFN/RBV can improve liver disease despite little or no viral response.