 |
|
|
| |
Amantadine Triple Therapy: interferon/ribavirin
|
| |
| |
In Thursday's opening oral session in the evening at EASL, a German research group (T Berg), reported on a randomized, controlled, placebo controlled study of triple therapy with amantadine and an induction regimen of interferon and ribavirin in 400 previously untreated patients. There has been much controversy on whether amantadine is useful as an additional therapy in a combination including interferon in treating HCV. Berg reviewed the mixed results from 6 randomized studies although the studies showing benefit he listed were mostly 3 month study results except for 1 study.
Patients were randomized to receive an induction interferon regimen: 9 million units of interferon daily for 2 weeks, followed by 6 million daily for 6 weeks, followed by 6 million 3 times per week until week 24. At week 24 patients started receiving 3 MIU 3 times per week. Treatment was for 48 weeks with a post-treatment 24 week follow-up period. Therapy was evaluated at week 24.
RESULTS: 167 were randomized to amantadine and 162 to placebo. The 2 patient groups had comparable characteristics before starting the study: age 42, 75 kg, ALT 62, HCV RNA 6 million (AMT)- 5 million (placebo), about 60% genotype 1, 25% stage 3-4 fibrosis. Using what appeared to be an ITT analysis 52% overall in the amantadine group had an SVR compared to 43% for the placebo group but the results were borderline statistically significant (p=0.055). For genotype 1 patients (n=255) 39% had a SVR with amantadine vs 31% with placebo, these results were not statistically significant (p=0.01). For non-1 genotype patients (n=145) 74% in the amantadine group vs 65% in the placebo group had an SVR, again not significant (p=0.18). Using an on-treatment analysis (this does not include patients who dropped off the study, only patients remaining on study drug) Berg reported no difference in response rate in the non-1 genotypes between those receiving amantadine or placebo. But for genotype 1 patients 51% receiving amantadine had <100 copies/ml at week 48 vs 40% receiving placebo (p=0.045), suggesting the relapse rate was high. Berg reported patients receiving amantadine and optimal RBV dose of >10.6 mg/kg (retrospective analysis) had a 64% SVR vs 50% receiving placebo (p=0.037).
The RBV dose reduction rate was 41% in the amantadine group vs 32% in the placebo group. The study authors concluded amantadine seems to have additional antiviral effect and should be studied further, but I was underwhelmed with these results.
|
|
| |
|
|
|
|
|
