2008, Number 4
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Ann Hepatol 2008; 7 (4)
Optimizing dosage and duration therapy for chronic hepatitis C «difficult-to-treat patients»
Ladero JM
Language: English
References: 22
Page: 392-394
PDF size: 104.75 Kb.
Text Extraction
Treatment response remains suboptimal for many patients with chronic hepatitis C, particularly those with genotype 1 and high levels of viremia. The efficacy of high-dose regimens of peginterferon α-2a and ribavirin was compared with conventional dose regimens in patients with features predicting poor treatment responses. Eligible treatment-naïve adults with genotype 1 infection, hepatitis C virus (HCV) RNA › 800,000 IU/mL and body weight › 85 kg were randomized to double-blind treatment with peginterferon α-2a at 180 or 270 microg/week plus ribavirin at 1,200 or 1,600 mg/day for 48 weeks (four regimens were evaluated). The primary endpoint was viral kinetics during the first 24 weeks of therapy. Among patients receiving peginterferon α-2a (270 microg/week) the magnitude of HCV RNA reduction was significantly greater than for patients randomized to the conventional dose of peginterferon α-2a (180 microg/week) for the pairwise comparison for ribavirin at 1,600 mg/day (P = 0.036) and numerically greater for the pairwise comparison for ribavirin at 1200 mg/day (P = 0.060). Patients randomized to the highest doses of peginterferon α-2a (270 microg/week) and ribavirin (1,600 mg/day) experienced the numerically highest rates of sustained virologic response (HCV RNA ‹ 50 IU/mL) and the lowest relapse rate (47% and 19%, respectively). The arm with the higher doses of both drugs was less well-tolerated than the other regimens.
Conclusion: Higher fixed doses of peginterferon alfa-2a (270 microg/week) and ribavirin (1600 mg/day) may increase sustained virologic response rates compared with lower doses of both drugs in patients with a cluster of difficultto-treat characteristics.
REFERENCES
Gambarin-Gelwan M, Jacobson IM. Optimal dose of interferon and ribavirin for treatment of chronic hepatitis C. J Viral Hepatitis 2008; 15: 623-33.
Davis GL,Wong JB, Hutchinson JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon a-2b plus ribaririn in patients with chronic hepatitis C. Hepatology 2003; 38: 645-52.
Poynard T, McHutchison J, Goodman Z, Ling, MH, Albrecht J. In an «à la carte» combination interferon a-2b plus ribavirin regime possible for the first line treatment in patients with chronic hepatitis C?. The ALGOVIRC Project Group. Hepatology 2000; 31: 211-8.
Zeuzem S, Fried MW, Reddy KR, Marcellin P, Diago M, Craxi A, et al. Improving the clinical relevance of pre-treatment viral load as a predictor of sustained virological response (SVR) in patients infected with hepatitis C genotype 1 treated with peginterferon a-2a (40 kDa) (PEGASYS) plus ribavirin (COPEGUS). Hepatology 2006; 44: 267A.
Fried MF, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL, Haüssinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon a-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 3 47: 975-82.
Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon a-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet 2001; 358: 958-65.
Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, et al. Peginterferon-a2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004; 140: 346-55.
Conjeevaram HS, Kleiner DE, Everhart JE, Hoofnagle JH, Zacks S, Afdhal NH et al. Race, insulin resistance and hepatic steatosis in chronic hepatitis C. Hepatology 2007; 45: 80-7.
McHutchison JG, Manns M, Patel K, Poynard T, Lindsay KL, Trepo C, et al. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology 2002; 123: 1061-9.
Fried MW, Jensen DM, Rodríguez-Torres M, Nyberg LM, Di Bisceglie AM, Morgan TR, et al. Improved outcomes in patients with hepatitis C with difficult –to-treat characteristics: randomized study of higher doses of Peginterferon a-2a and ribavirin. Hepatology 2008; 48: 1033-43.
Mimidis K, Papadopoulos VP, Elefsiniotis I, Koliouskas D, Ketikoglou I, Paraskevas E, et al. Hepatitis C virus survival curve analysis in naïve patients treated with peginterferon alpha-2b plus ribavirin. A randomized controlled trial for induction with high doses of peginterferon and predictability of sustained viral response from early virologic data. J Gastrointestin Liver Dis 2006; 13: 213-9.
Enomoto S, Tamai H, Oka M. Shingaki N, Shiraki T, Takeuchi M, et al. Potent induction therapy with interferon and ribavirin combination therapy does not achieve a higher sustained virological response rate in chronic hepatitis C with genotype 1b and high hepatitis C virus RNA level. Hepatol Res 2007; 37: 692-700.
Gelderblom HC, Zaaijer HL, Dijkgraaf MG, Van der Meer J, Weegink CJ, et al. Prediction of virologic response in difficult-to-treat chronic hepatitis C patients during high-dose interferon induction therapy. Scand J Gastroenterol 2008; 43: 857-69.
Berg T, Von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, et al. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-a-2a plus ribavirin. Gastroenterology 2006; 130: 1086-97.
Ladero JM, López-Alonso G, Devesa MJ, Cuenca F, Agreda M, Ortega L, et al. «12 weeks’ stopping rule» in the treatment of genotype 1 chronic hepatitis C: Two prognostic categories under the same label? Scand J Gastroenterol. 2008 Apr 1:1-5
Pearlman BL, Eleven C, Saifee S. Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis C genotype 1-infected slow responders. Hepatology 2007; 46: 1688-94.
Arase Y, Suzuki F, Sezaki H, Suzuki Y, Kawamura Y, Kobayashi M, et al. Suitable treatment period in patients with virological response during combination therapy of peginterferon and ribavirin for chronic hepatitis C. Intern Med 2008; 47: 1301-7.
Mangia A, Minerva N, Bacca D, Cozzolongo R, Ricci GL, Carretta V, et al. Individualized treatment duration for hepatitis C genotype 1 patients: A randomized controlled trial. Hepatology 2008; 47: 43-50.
Marcellin P, Heathcote EJ, Craxi A. Which patients with genotype 1 chronic hepatitis C can benefir from prolonged treatment with the «accordion» regimen? J Hepatol 2007; 47: 580-7.
Pearlman BL. Extended-therapy duration for chronic hepatitis C, genotype 1: the long and the short of it. World J Gastroenterol 2008; 14: 3621-7.
Dienstag J, McHutchison JG. American Gastroenterological Association medical position statement on the management of Hepatitis C. Gastroenterology 2006; 130: 225-30.
Documento de consenso de la AEEH sobre el tratamiento de las infecciones por los virus de las hepatitis B y C. Gastroenterol Hepatol 2006; 29 (supl. 2): 216-30.