May 20-23, 2001
High Dose Induction Therapy With Consensus Interferon Followed By Combination Therapy With Ribavirin For Treatment-Naive Hepatitis C Patients
Stephan Kaiser, Christian Kreysel, Holger Hass, Michael Gregor, Univ of Tuebingen, Tuebingen Germany
Interferon treatment in combination with ribavirin has an efficacy in patients with chronic hepatitis C with sustained response rates of about 40%: However, response rates in genotype 1 patients with high viral load are considerably lower. Recent studies have shown improved response rates using consensus interferon (CIFN) especially in genotype 1 and high viral load patients.
In the present study, the efficacy of a CIFN induction therapy followed by CIFN / ribavirin combination treatment in naive patients with chronic hepatitis C is evaluated. 147 patients of a total of 300 have so far been included. All patients had elevated ALT values and were viremic. Histologic confirmation of chronic inflammation by liver biopsy was obtained in all patients. Patients (n=105) are treated with CIFN with 18 ug QD for 4 weeks, followed by 9 ug QD for 8 weeks.
In one treatment group patients (n=42) receive CIFN 27 ug QD for 4 weeks, followed by 8 weeks of CIFN 18 ug QD. Thereafter, treatment is continued in all treatment groups with CIFN at a dose of 9 ug QD or TIW with or without ribavirin (at 7.5 or 15 mg/kg/d) for another 36 weeks.
After 12 weeks of therapy, a primary response with undetectable serum HCV-RNA was observed in 73% of patients in the CIFN 18/9 ug QD group and in 86% in the CIFN 27/18 ug group. Interestingly, a negative HCV-RNA could be shown in 63% of all patients treated with CIFN 18/9 ug QD already after 2 weeks of therapy.
In the group of patients treated with CIFN 27/18 ug a negative PCR was demonstrated in 74% at 2 weeks of therapy. Within the first 4 weeks of therapy a significant rise in ALT levels was noted in 67% of all patients. This effect was observed more frequently with the higher dose of CIFN given in the treatment group with CIFN 27/18 ug, however, did not lead to any dose reduction or discontinuation of therapy.
Due to side effects the CIFN had to be reduced in 11% of patients and discontinued in 6% of patients. All genotype 2 and 3 patients so far responded to therapy, whereas 65% of genotype 1 patients responded. Furthermore, CIFN may even offer acceptable response rates as a monotherapy in hepatitis C patients, where ribavirin is not tolerated or contraindicated. The further follow-up of this study will show the additional effect of ribavirin and whether the high initial response rates will translate into corresponding sustained response rates.
Preliminary HCV RNA response at week 24 in naïve patients receiving daily CIFN (Consensus IFN) + RBV
CIFN 27/18/9 ug once daily + RBV 1000/1200 mg once daily:
CIFN 18/9 ug once daily / 9 ug TIW + RBV 1000/1200 mg once daily
HCV RNA response at week 24 in naïve patients treated with CIFN +/- RBV
* all patients with initial treatment of 18/8 ug CIFN once daily, then 9 ug CIFN tiw
Kaiser reported the 1st phase viral load decline was greater and more prolonged when using the high dose CIFN of 27 (3 logs) vs the 18 dose (2 logs)
Kaiser concluded CIFN with a high (up to 27 ug) and daily dose regimen is moderately well-tolerated for at least 12 weeks of initial therapy. With the dose regimens used, transient lab abormalities (ALT elevations) ocurred, not leading to clinically relevant observations. WBC and platelet depressions seem to occur as frequent with CIFN 18 ug/day and more commonly with CIFN ug/day induction than with IFN-2b 10 MU/day. If these data hold up this regimen may be useful in difficult to treat patients. Patients with genotype 1 treated with 27 ug show up to 5 log decline in 2 days. 27 ug is not significantly better than 18 ug for patients with HCV genotype 2 or for patients with genotype 2 with low viral load. For patients with genotype 1 and high baseline viral load 27 ug CIFN shows better early response than 18 ug CIFN.
Events Week 12
|27/18 Dose (n=39)||18/9 Dose (n=123)|