|
|
|
|
Individualized treatment of hepatitis C patients with Rebetron® Bennet D. Cecil, MD Louisville VAMC AASLD Abstract 1844 Hepatology, Vol 30, No. 4, Pr 2, 1999 621A Clinical trials are essential to study the efficacy and safety of new therapies for chronic hepatitis, but standard doses of medications cannot replace tailored therapy for individual patients. The dose of interferon must be adjusted as needed in hepatitis C patients for an optimal response as the insulin dose is adjusted in diabetics. The HCV-RNA should be checked at 4 weeks instead of waiting 24 weeks to see if the interferon dose was correct. Stopping therapy if the HCV-RNA is detectable at 24 weeks after using a weak dose of interferon is illogical, wasteful and unnecessarily demoralizing to patients enduring significant side effects from treatment. Rebetron® is a major advance in the treatment of hepatitis C with a 41% sustained response rate in patients treated for 48 weeks. Subgroup analysis has revealed favorable and unfavorable patient characteristics, which help to guide therapy. However, the most important factor has been largely unrecognized-the individual patient’s HCV-RNA response to treatment. For a sustained response to occur with Rebetron® the patient must be prescribed an adequate dose of interferon along with 600-1,200mg per day of ribavirin to make the HCV-RNA undetectable during treatment. It must stay undetectable for perhaps several months if relapse is to be prevented when treatment is stopped. 33 veterans with chronic hepatitis C, several with biopsy proven cirrhosis, are being treated at the Louisville VAMC with Rebetron®. The primary objective is to obtain an undetectable HCV-RNA during treatment and to keep it undetectable for several months before stopping treatment. HCV-RNA by PCR was measured in each patient before treatment and during treatment, usually at 4 weeks. If the repeat HCV-RNA was not down by more than 90% the dose of Intron A was usually increased to 3 million units per day and up to 6 million units per day. Repeat HCV-RNA will be measured at 24 weeks and a decision will be made whether to stop treatment or increase the dose. The determination of genotype is costly, unnecessary and does not improve management of individual patients. 14 of 33 patients (42%) have undetectable HCV-RNA by PCR during treatment. 12 of 33 patients (36%) are partial responders with a 96% fall in their HCV-RNA during therapy (mean pretreatment 1,724,337 copies/ml to mean during treatment 70,704 copies/ml). Most are expected to have undetectable HCV-RNA by 24 weeks. 7 of 33 patients (22%) were d/c from Rx, one with confusion, one with severe psoriasis and five because of a poor HCV-RNA response to treatment. Conclusions: 1.Individualized Rebetron® therapy using higher interferon doses than 3MU TIW in selected patients results in an excellent treatment response in the majority 26 of 33 (78%) VA patients, several with biopsy proven cirrhosis. 2.Measuring the HCV-RNA at 4 weeks is very helpful in guiding adjustment of the interferon dose in selected patients. 3.Higher interferon doses are associated with a higher virologic response rate during treatment and greater toxicity. 4.Genotype determination is expensive and unnecessary with this approach to treatment. The sustained response rate is unknown. 5.The dose and duration of Rebetron® treatment should be individualized for each patient. Supported in part by Integrated Therapeutics Group INC |