Induction Pegylated Interferon Alfa-2a and High Dose Ribavirin Do Not Increase SVR in Heavy Patients With HCV Genotype 1 and High Viral Loads

Gastroenterology
Volume 139, Issue 6 , Pages 1972-1983, December 2010

K. Rajender Reddy, Mitchell L. Shiffman, Maribel Rodriguez–Torres, Hugo Cheinquer, Djamal Abdurakhmanov, Igor Bakulin, Viacheslav Morozov, Giovanni Faria Silva, Natalia Geyvandova, Carol Stanciu, Michael Rabbia, Michael McKenna, James A. Thommes, Stephen A. Harrison, PROGRESS Study Investigators

Received 28 May 2010; accepted 17 August 2010. published online 06 September 2010.

Abstract

Background & Aims
Patients infected with hepatitis C virus (HCV) genotype 1, body weight ≥85 kg, and high baseline viral load respond poorly to standard doses of pegylated interferon (peginterferon) and ribavirin. We evaluated intensified therapy with peginterferon alfa-2a plus ribavirin.

Methods
This double-blind randomized trial included HCV genotype 1-infected outpatients from hepatology clinics with body weight ≥85 kg and HCV RNA titer ≥400,000 IU/mL. Patients were randomized to 180 μg/wk peginterferon alfa-2a for 48 weeks plus 1200 mg/day ribavirin (standard of care) (group A, n = 191) or 1400/1600 mg/day ribavirin (group B, n = 189). Additional groups included 360 μg/wk peginterferon alfa-2a for 12 weeks then 180 μg/wk peginterferon alfa-2a for 36 weeks plus 1200 mg/day ribavirin (group C, n = 382) or 1400/1600 mg/day ribavirin (group D, n = 383). Follow-up lasted 24 weeks after treatment.

Results
Sustained virologic response rates (HCV RNA level <15 IU/mL at end of follow-up) in groups A, B, C, and D were 38%, 43%, 44%, and 41%, respectively. There were no significant differences among the 4 groups or between pooled peginterferon alfa-2a regimens (A + B vs C + D: odds ratio [OR], 1.08; 95% confidence interval [CI], 0.83–1.39; P = .584) or pooled ribavirin regimens (A + C vs B + D: OR, 1.00; 95% CI, 0.79–1.28; P = .974).

Conclusions
In patients infected with HCV genotype 1 who are difficult to treat (high viral load, body weight ≥85 kg), a 12-week induction regimen of peginterferon alfa-2a and/or higher-dose ribavirin is not more effective than the standard regimen.

Keywords: Chronic Hepatitis C, Tolerability of High-Dose Pegylated Interferon, Steatosis and Response to HCV Therapy, Tolerability of High-Dose Ribavirin

Source