Retreatment with interferon plus ribavirin of chronic hepatitis C non-responders to interferon monotherapy: a meta-analysis of individual patient data

Abstract

Background and aims: Retreatment with a combination of α interferon (IFN) plus ribavirin of patients with chronic hepatitis C who did not respond to IFN monotherapy has not been assessed in large controlled studies. Methods: To assess the effectiveness and tolerability of IFN/ribavirin retreatment of non-responders to IFN and to identify predictors of complete (biochemical and virological) sustained response, we performed a meta-analysis of individual data on 581 patients from 10 centres. Retreatment with various IFN schedules (mean total dose 544 mega units) and a fixed ribavirin dose (1000-1200 mg/daily depending on body weight) was given for 24-60 (mean 39.5) weeks. Results: Biochemical end of treatment and sustained responses were observed in 271/581 (46.6%; 95% confidence interval (CI) 42.6-50.7%) and in 109/581 (18.7%; 95% CI 15.6-22.0%) cases, respectively. Two hundred and six of 532 patients (38.7%; 95% CI 34.6-42.9%) had an end of treatment complete response to retreatment while a complete sustained response occurred in 88 of 559 (15.7%; 95% CI 12.8-18.8%). Fifty four of 581 patients (9.2%; 95% CI 7.0-11.7%) stopped retreatment due to adverse effects. By logistic regression, complete sustained response was predicted independently by age <45 years (p=0.04), by normal pretreatment γ-glutamyltransferase levels (p=0.01), and by a second course total IFN dose of at least 432 mega units (p=0.008). Conclusions:The overall low probability of effectiveness argues against indiscriminate retreatment of all IFN monotherapy non-responders with IFN/ribavirin. Patients less than 45 years old with normal γ-glutamyltransferase levels who were retreated with high dose long course combination therapy had a complete sustained response rate of 30%.

Factors contributing to ribavirin dose reduction due to anemia during interferon alfa2b and ribavirin combination therapy for chronic hepatitis C

“…In previous studies, the mean patient age was 41-45 years, 7,8,[10][11][12][13][14]23 lower than that in our study. Although subpopulations according to patient age are not known for previous studies, our results indicated that the subpopulation of older patients was greater in our study than in these earlier reports.…”

“…7,8,14,23 The proportion of patients requiring ribavirin dose reduction was reported to be 6% to 20%. [7][8][9][10]23 In our study, the mean maximal decrease was 4.0 g/dl (range, 0.2-7.6 g/dl), which was greater than those reported previously. This result suggests that patients with lower baseline Hb levels will decrease to levels of less than 10 g/dl more easily compared with those with higher baseline Hb levels, and therefore will more frequently require ribavirin dose reduction.…”

“…With respect to the IFN dose, the treatment schedule used in our study differed from that in other studies. Patients were administered 3 MU three times a week in other studies, 7,8,[10][11][12][13][14]23 whereas our patients were administered 6 MU every day for the first 2 weeks (induction therapy) and then they received 6 MU three times a week for the subsequent 22 weeks. The difference in dose apparently influenced the rate of reduction of ribavirin dose and the reduction in Hb level.…”

Peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy

“…A meta-analysis that evaluated the efficacy of conventional IFN and ribavirin combination therapy in previous nonresponders reported only 13% SVR, thus indicating the need for better therapeutic options [8].…”

Recombinant Interferon-Beta-1a Plus Ribavirin for the Treatment of Chronic HCV Infection: A Prospective, Randomized, Comparative Pilot Study

“…8 Re-treatment with similar regimen after the initial failure is not an optimal choice as the outcome is relatively poor. 9,10 Furthermore, the IFN-α based treatment is not without side effects. Patients often have to discontinue treatment due to intolerable side effects or reduce the treatment dosages to minimize such effects.…”