NEW YORK -- Giving bigger ribavirin doses to heavier hepatitis C patients appears to result in better outcomes, especially for African Americans, researchers here said.
NEW YORK, Oct. 2 -- Giving bigger ribavirin doses to heavier hepatitis C patients appears to result in better outcomes, especially for African Americans, researchers here said.
The finding, from a prospective randomized trial of more than 5,000 treatment-nave patients, supports the idea of so-called true weight-based dosing of ribavirin, in combination with pegylated interferon alfa-2b, according to Ira M. Jacobson, M.D., of Weill Cornell Medical College, and colleagues.
The combination of the two drugs has been used to treat HCV infection since 2001, with ribavirin given at 1,000 mg a day for patients who weigh less than 75 kg and 1,200 for those who weigh 75 kg or more, Dr. Jacobson and colleagues reported in the October issue of Hepatology.
But in this study, patients were randomized to a flat dose of 800 mg/day, regardless of weight, or to one of several doses adjusted for weight -- 800 mg for patients weighing less than 65 kg, 1,000 mg for patients from 65 to 85 kg, 1,200 mg for those from 85 to 105 kg, and 1,400 mg for patients from 105 to 125 kg.
Patients with genotypes G1, G4, G5, and G6 were treated for 48 weeks and followed for another 24. The primary endpoint was sustained virologic response, defined as less than 125 IU per milliliter of serum of HCV viral RNA, at the end of follow-up.
Patients with genotypes G2 and G3 -- regarded as easier to treat than the other types -- were treated for 24 or 48 weeks.
The study showed that patients in the weight based-arm did better, with a sustained virologic response of 44.2% compared to 40.5% for those in the flat-dose arm. The difference was significant at P=0.008.
Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P
The issue of treating African Americans is important, the researchers noted, because the prevalence of HCV infection is higher in African Americans than in other ethnic groups, and up to 90% of infected African Americans have genotype G1a or G1b -- both associated with lower response to therapy.
Dr. Jacobson and colleagues noted that even in this study, African Americans had a lower response to treatment, although those in the weight-based arm did better.
Unexpectedly, the researchers said, heavier African Americans in the weight-based arm appeared to do better. The rate of sustained virologic response was 31% for those weighing between 105 and 125 kg, compared with 22% for those between 85 and 015 kg, and 13% for those between 65 and 85 kg.
The researchers said they had no clear explanation for the phenomenon.
The study "adds significantly to our understanding of interferon therapy in African-American patients," commented Steven-Huy Han, M.D., of the University of California Los Angeles and Jason Smith, PharmD, of the Greater Los Angeles Veterans Healthcare Administration Hospital, in an accompanying editorial.
They noted that the findings concerning this "difficult-to-treat population" arise from a secondary evaluation that was not powered for statistical analysis.
Nonetheless, they said, "many of their insights deserve a thoughtful discussion."
On the other hand, they said, the overall study shows that "the traditional notion that ribavirin dosage should be fixed has now been sidelined by the idea that we should tailor ribavirin dosing to our patients."
Drs. Han and Smith reported no potential conflicts.