Retreatment of patients with chronic hepatitis C not responding to interferon/ribavirin combination therapy with daily interferon plus ribavirin plus amantadine

Abstract

There is currently no accepted therapeutic regimen for patients with chronic hepatitis C who failed to respond to standard combination treatment with interferon-alpha plus ribavirin. We investigated triple combination treatment with induction dosing of interferon-alpha plus ribavirin plus amantadine in these difficult-to-treat patients. Nonresponders (n = 67), breakthroughs (n = 16) and relapsers (n = 19) to previous interferon/ribavirin combination treatment of at least 6 months were included. For the first 16 weeks, patients received interferon-alpha2a 6 MU daily, ribavirin 800-1200 mg/d, and amantadine 200 mg/d. In cases of undetectable HCV RNA at week 12, treatment was continued with interferon-alpha2a 6 MU every other day and the same doses of ribavirin and amantadine until week 48. In cases of HCV RNA positivity at week 12, treatment was stopped. A total of 102 patients were enrolled (80%: genotype 1, 19%: cirrhosis). HCV RNA was negative in 35/102 patients (34%) at week 12 and in 27/ 102 patients (26%) at the end of treatment. Virological response was sustained in 15/102 patients (15%). On-treatment virological response was higher in previous relapsers/breakthroughs than in previous nonresponders (week 12: 49% vs. 27%, p < 0.05; week 48: 46% vs. 16%, p < 0.01) but no such difference was found for sustained virological response (20% vs. 12%, NS). In conclusion, triple combination treatment with daily interferon-alpha plus ribavirin plus amantadine for 3 months can induce virological response in a considerable number of nonresponders/relapsers to previous dual combination treatment, but the sustained virological response rate remains low.

Randomized, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD) plus ribavirin with or without amantadine in treatment-naïve patients with chronic hepatitis C genotype 1 infection

“…In previously untreated patients, the addition of amantadine has either improved the outcomes of interferon monotherapy [2,3] or has had no beneficial effect [4][5][6][7]. Although meta-analysis data indicate that interferon plus amantadine therapy may be an alternative regimen for patients who cannot tolerate ribavirin [8], the efficacy of triple therapy, both as initial therapy or for the treatment of non-responders to interferon plus ribavirin, is uncertain [9][10][11][12][13][14][15][16][17][18].…”

Optimizing Treatment Outcomes in Chronic Hepatitis C: Management of Non-Response

“…The efficacy of triple combination therapy regimens, whereby a third agent with a different mode of action is added to standard therapy, has recently been assessed among previous non-responders and those with 'difficult to treat' characteristics. Studies using a triple combination with amantadine (an antiviral agent) have generally shown a modest or no added benefit compared with standard therapy [29,30,[81][82][83][84]. However, a recent meta-analysis of 38 randomized studies suggested some benefit in previous non-responders, but no notable effect in treatment-naive or relapser patients [27].…”

Standard interferon-alpha in combination with ribavirin for hepatitis C patients with advanced liver disease and thrombocytopenia

“…Standard IFN-a, although less efficacious than pegylated IFN, allows better control of platelet and white blood cell counts, because of different pharmacokinetics with a shorter half-life. In previous studies, daily administration of IFN was well tolerated [18]. Thus, therapy with low-dose standard IFNs with a later dose increase -an 'accelerating dose regimen' [19] -may be beneficial in the setting of these difficult-to-treat patients with cirrhosis.…”