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Cited by 3 publications
References 38 publications
We thank Drs. Han and Smith for their thoughtful editorial 1 that accompanied our 2 papers describing results of the WIN-R (WeightBased Dosing of Peginterferon alfa-2b and Ribavirin) trial, 2,3 in which patients with chronic hepatitis C were treated with peginterferon (PEG-IFN) alfa-2b 1.5 g/kg/week plus flat-dose (FD; 800 mg/day) or weight-based dose (WBD; 800-1400 mg/day) ribavirin (RBV). The authors appropriately focused on the importance and superiority of WBD RBV in hepatitis C virus genotype 1-infected patients and provided an excellent review of the treatment of African Americans. However, several points require correction or clarification.The authors state that before 2001, the accepted dose of RBV was 800 mg. Actually, RBV was approved for use with standard, unmodified interferon alfa-2b at doses of 1000-1200 mg in the late 1990s. Later, RBV was approved in the United States for use with PEG-IFN alfa-2b at a dose of 800 mg; currently, the approved dose is 800-1200 mg, based on body weight, in the rest of the world. When using PEG-IFN alfa-2a, the approved RBV dose is 1000-1200 mg in the United States and abroad. Therefore, the statement "currently approved therapies recommend 'standard' WBD RBV in combination with PEG-IFN alfa-2a or 2b" is inaccurate. In fact, there is no "standard" WBD of RBV. A main objective of the WIN-R trial was to evaluate whether the regimen approved in many countries-PEG-IFN alfa-2b 1.5 g/kg/week plus WBD RBV (800-1200 mg/day)-was superior to the U.S.-approved regimen of PEG-IFN alfa-2b 1.5 g/ kg/week plus RBV 800 mg/day. Further, because there are many heavy (Ͼ105 kg) patients in the United States, WIN-R also evaluated a novel, 1400-mg/day RBV dosage, which is not approved anywhere. Although not mentioned in the editorial, we reported equivalent sustained virologic response (SVR) rates in patients weighing Ͼ105 kg and receiving RBV 1400 mg/day compared with patients weighing Յ105 kg and receiving RBV 800-1200 mg/day, as well as equivalent hematologic safety across weight categories. We regard this as an important additional finding of the study that should lead to consideration of RBV 1400 mg in heavy patients weighing Ͼ105 kg.The authors of the editorial ascribed to us a suggestion, which we did not make, that the WBD range of RBV used in our study was superior to that used in the study of Hadziyannis et al.,4 in which RBV 800 mg/day was compared with RBV 1000-1200 mg/day (both in combination with flat-dose PEG-IFN alfa-2a [180 g/week]), based on a greater relative difference in SVR rates between the FD and WBD groups in our study. We made this comparison only with regard to African Americans with genotype 1 infection in the WIN-R trial, 3 in whom the increment in SVR with WBD RBV was greater than in the overall patient cohorts of either study. [2][3][4] The intent in our primary paper 2 in citing the study by Hadziyannis et al. 4 was to underscore the demonstration in the WIN-R trial that a broad WBD range of RBV, combined with weight-based PEG-IFN alfa-2b, produces equivalen...
We thank Drs. Han and Smith for their thoughtful editorial 1 that accompanied our 2 papers describing results of the WIN-R (WeightBased Dosing of Peginterferon alfa-2b and Ribavirin) trial, 2,3 in which patients with chronic hepatitis C were treated with peginterferon (PEG-IFN) alfa-2b 1.5 g/kg/week plus flat-dose (FD; 800 mg/day) or weight-based dose (WBD; 800-1400 mg/day) ribavirin (RBV). The authors appropriately focused on the importance and superiority of WBD RBV in hepatitis C virus genotype 1-infected patients and provided an excellent review of the treatment of African Americans. However, several points require correction or clarification.The authors state that before 2001, the accepted dose of RBV was 800 mg. Actually, RBV was approved for use with standard, unmodified interferon alfa-2b at doses of 1000-1200 mg in the late 1990s. Later, RBV was approved in the United States for use with PEG-IFN alfa-2b at a dose of 800 mg; currently, the approved dose is 800-1200 mg, based on body weight, in the rest of the world. When using PEG-IFN alfa-2a, the approved RBV dose is 1000-1200 mg in the United States and abroad. Therefore, the statement "currently approved therapies recommend 'standard' WBD RBV in combination with PEG-IFN alfa-2a or 2b" is inaccurate. In fact, there is no "standard" WBD of RBV. A main objective of the WIN-R trial was to evaluate whether the regimen approved in many countries-PEG-IFN alfa-2b 1.5 g/kg/week plus WBD RBV (800-1200 mg/day)-was superior to the U.S.-approved regimen of PEG-IFN alfa-2b 1.5 g/ kg/week plus RBV 800 mg/day. Further, because there are many heavy (Ͼ105 kg) patients in the United States, WIN-R also evaluated a novel, 1400-mg/day RBV dosage, which is not approved anywhere. Although not mentioned in the editorial, we reported equivalent sustained virologic response (SVR) rates in patients weighing Ͼ105 kg and receiving RBV 1400 mg/day compared with patients weighing Յ105 kg and receiving RBV 800-1200 mg/day, as well as equivalent hematologic safety across weight categories. We regard this as an important additional finding of the study that should lead to consideration of RBV 1400 mg in heavy patients weighing Ͼ105 kg.The authors of the editorial ascribed to us a suggestion, which we did not make, that the WBD range of RBV used in our study was superior to that used in the study of Hadziyannis et al.,4 in which RBV 800 mg/day was compared with RBV 1000-1200 mg/day (both in combination with flat-dose PEG-IFN alfa-2a [180 g/week]), based on a greater relative difference in SVR rates between the FD and WBD groups in our study. We made this comparison only with regard to African Americans with genotype 1 infection in the WIN-R trial, 3 in whom the increment in SVR with WBD RBV was greater than in the overall patient cohorts of either study. [2][3][4] The intent in our primary paper 2 in citing the study by Hadziyannis et al. 4 was to underscore the demonstration in the WIN-R trial that a broad WBD range of RBV, combined with weight-based PEG-IFN alfa-2b, produces equivalen...
Background Pegylated interferon/ribavirin combination is currently the standard treatment for chronic hepatitis C virus (HCV) infection. Body weight adjustment of ribavirin is crucial for response. However, previous studies found no relation between ingested dose and plasma concentration. The aim of this study was to define the ribavirin trough plasma concentration at week 4 (W4) associated with sustained virological response (SVR). Methods Thirty-one HCV genotype 1 patients (8 naive and 23 non-responders to a previous pegylated interferon/ribavirin therapy) were treated with pegylated interferon/ribavirin and assessed by HPLC for ribavirin plasma concentration at W4. Results Eleven patients (35%) achieved SVR, whereas 20 (65%) were non-responders. The median ribavirin plasma concentration at W4 (1.90 mg/l) varied from 1.62 mg/l in patients with subsequent non-response to 2.28 mg/l in sustained responders ( P=0.007). Receiver operating characteristic curve analysis indicated that the 2.01 mg/l threshold gave the best sensitivity and specificity (73% and 80%, respectively, area under the curve=0.80; P=0.007). Sixty-seven percent of patients with median ribavirin plasma concentration >2 mg/l achieved SVR versus only 16% below this level ( P=0.007). Multivariate regression analysis indicated that a ribavirin plasma concentration >2 mg/l at W4 was associated with SVR independent of gender, age, weight, baseline viral load and response to previous therapy. Conclusion These results, which remain to be confirmed in large clinical trials, highlight the potential relevance of ribavirin plasma level monitoring at an early stage of treatment. This monitoring could be of help in guiding antiviral therapy by offering dose adjustment in patients with ribavirin plasma level below the 2 mg/l threshold.
Since 1995, after the generalization of highly active antiretroviral therapy (HAART), HCV coinfection in patients with HIV has become a clinical problem of first magnitude. In fact, currently, HCV coinfection is the primary cause of morbi-mortality of AIDS patients in many hospitals. As a consequence, a significant number of clinical trials have been carried out during the past 8-10 years on HCV/HIV-coinfected patients, and have been coincident that the use of pegylated interferon (PEG-IFN) plus ribavirin should be now the gold standard for treating these patients. Various prospective, randomized studies have reached the conclusion that PEG-IFN-alpha(2b) plus ribavirin achieves HCV cure rates in approximately 50% of all patients, together with important clinical consequences, since hepatic illness progression stops or even reverts. Although adverse events are extremely common with this combined treatment, it is also true that their handling by experts means that only 10-15% of patients must abandon treatment.
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