A multidisciplinary team from the USA assessed the efficacy and safety of interferon and ribavirin vs. interferon alone for treatment of patients with chronic hepatitis C, who previously did not respond to interferon monotherapy.
The researchers reviewed relevant publications (identified from MEDLINE 1960-December 1999) and specialty journals, and sought input from clinical hepatology experts.
Of 50 identified studies, 12 trials (941 patients) were included in the analysis.
Interferon alfa-2a/2b and ribavirin, 1-1.2g/d, give an 18% virological response
Two investigators reviewed trials independently for methods, inclusion and exclusion criteria, and outcomes.
Abstracted data included study- and patient-characteristics and virological, biochemical, and histological outcomes. A quality evaluation questionnaire was used to score studies.
The pooled virological response rate for combination therapy was found to be 14 per cent, with a risk difference favoring combination therapy of 7 per cent.
Use of interferon alfa-2a/2b and ribavirin, 1000 to 1200 mg/d, was associated with a pooled virological response rate of 18 per cent and a risk difference of 16 per cent.
When interferon alfa-n/n3 and a lower dosage of ribavirin (600-800 mg/d) were used, the risk difference was 0 per cent.
The researchers found that combination therapy was associated with more adverse effects and an increased rate of discontinuation of treatment compared with interferon monotherapy.
Dr Kristin Cummings said on behalf of the group, "For chronic hepatitis C that is non-responsive to prior interferon monotherapy, combination therapy is more effective than re-treatment with interferon alone.
"Response rates remain less than 20 per cent even in the most responsive subgroups, demonstrating a need for better therapeutic options."
In an accompanying editorial, Professor Raymond Koff writes, "The mechanisms responsible for non-response are poorly understood. Further studies are needed to understand the mechanism of interferon resistance and to permit the design of therapeutic regimens that can bypass or overcome non-responsiveness."