991 Final Results of the Ideal (Individualized Dosing Efficacy Versus Flat Dosing to Assess Optimal Pegylated Interferon Therapy) Phase Iiib Study

Sulkowski, Mark S.; Läwitz, E.; Shiffman, M.; Muir, Andrew J.; Galler, Greg; McCone, Jonathan; Nyberg, L; Lee, W.M.; Ghalib, R.; Schiff, E.; Galati, Joseph; Bacon, B.; Davis, Mat D.; Mukhopadhyay, Pralay; Noviello, Stephanie; Pedicone, Lisa D.; Albrecht, J.; McHutchison, J.

doi:10.1016/s0168-8278(08)60993-9

Cited by 41 publications

(41 citation statements)

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“…In addition, anxiety and depression impair the level and activity of B cells, T cells, and NK cells [55] . No differences in depression rates were observed by Neri et al [56] comparing PEGylated-α 2a and PEGylated-α 2b, and this finding has recently been confirmed in the large randomized comparison trial 'IDEAL' [57] . Depression and anxiety of significant severity can adversely effect compliance and tolerance to medication.…”

Section: Depressionmentioning

confidence: 68%

Hepatitis C comorbidities affecting the course and response to therapy

El-Zayadi¹

2009

WJG

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Several studies have demonstrated that the outcome of chronic hepatitis C (CHC) infection is profoundly influenced by a variety of comorbidities. Many of these comorbidities have a significant influence on the response to antiviral therapy. These comorbidities negatively affect the course and outcome of liver disease, often reducing the chance of achieving a sustained virological response with PEGylated interferon and ribavirin treatments. Comorbidities affecting response to antiviral therapy reduce compliance and adherence to inadequate doses of therapy. The most important comorbidities affecting the course of CHC include hepatitis B virus coinfection, metabolic syndrome, and intestinal bacterial overgrowth. Comorbidities affecting the course and response to therapy include schistosomiasis, iron overload, alcohol abuse, and excessive smoking. Comorbidities affecting response to antiviral therapy include depression, anemia, cardiovascular disease, and renal failure.

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Section: Depressionmentioning

confidence: 68%

Hepatitis C comorbidities affecting the course and response to therapy

El-Zayadi¹

2009

WJG

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“…Only preliminary data from two different prospective, comparative studies on HCV-monoinfected patients have been reported recently. 21,22 Therefore, we aimed to prospectively compare the efficacy and safety, in terms of SVR and adverse events, of PEG 2b plus RBV versus PEG 2a plus RBV in previously untreated HCV patients co-infected with HIV.…”

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confidence: 99%

Randomized trial comparing pegylated interferon α-2b versus pegylated interferon α-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients

et al. 2008

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. At baseline, both groups were well balanced: 73% male; 63% HCV genotype 1 through 4; 29% had fibrosis index of 3 or greater. The overall SVR was 44% (42% PEG 2b versus 46% PEG 2a, P ‫؍‬ 0.65). Among genotypes 1 through 4, SVRs were 28% versus 32% (P ‫؍‬ 0.67) and 62% versus 71% (P ‫؍‬ 0.6) in genotypes 2 through 3 for PEG 2b and PEG 2a, respectively. Early virological response (EVR; >2 log reduction from baseline or negative HCV-RNA at week 12) was 70% in the PEG 2b group and 80% in the PEG 2a group (P ‫؍‬ 0.13), reaching a positive predictive value of SVR of 64% and a negative predictive value of 100% in both arms. Side effects were present in 96% of patients but led to treatment discontinuation in 10% of patients (8% on PEG 2b and 13% on PEG 2a, P ‫؍‬ 0.47). Conclusion: In patients with HIV, HCV therapy with PEG 2b or PEG 2a plus RBV had no significant differences in efficacy and safety. (HEPATOLOGY 2009;49:22-310.)

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“…The IDEAL (Individualized Dosing Efficacy vs. Flat Dosing to Assess Optimal Pegylated Interferon Therapy) study has shown that the latter regimen delivers more RBV to patients than an 800-mg to 1400-mg dosing regimen. 14 Thus, it is likely that the patients in the METRO study, including those in the control arm, received more RBV than those in the study of Marcellin et al 10 Therefore, to the extent that the scientific rationale for use of MMPD is based on improving the effects of RBV, it may be that by receiving less RBV, the patients in the prior study had a greater capacity to show an increased RBV effect (in other words, they had more room for improvement). Finally, it is not uncommon for drugs, such as MMPD, that have demonstrated positive signals in small studies to fail to provide definitive benefits, in this case improved SVR, in larger-scale studies.…”

Section: Discussionmentioning

confidence: 99%

Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders

et al. 2009

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on behalf of the MErimepodib TRiple cOmbination (METRO) study group Merimepodib (MMPD) is an orally administered, inosine monophosphate dehydrogenase inhibitor that has shown antiviral activity in nonresponders with chronic hepatitis C (CHC) when combined with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) and ribavirin (RBV). We conducted a randomized, double-blind, multicenter, phase 2b study to evaluate the antiviral activity, safety, and tolerability of MMPD in combination with Peg-IFN-alfa-2a and RBV in patients with genotype 1 CHC who were nonresponders to prior therapy with Peg-IFN and RBV. Patients received 50 mg MMPD, 100 mg MMPD, or placebo every 12 hours, in addition to Peg-IFN-alfa-2a and RBV, for 24 weeks. Patients with a 2-log or more decrease from baseline or undetectable hepatitis C virus (HCV) RNA levels at week 24 were then eligible to continue Peg-IFN-alfa-2a and RBV for a further 24 weeks, followed by 24 weeks of follow-up. The primary efficacy endpoint was sustained virological response (SVR) rate at week 72 in all randomized patients who received at least one dose of study drug and had a history of nonresponse to standard therapy. A total of 354 patients were randomized to treatment (117 to placebo; 119 to 50 mg MMPD; 118 to 100 mg MMPD), and 286 completed the core study. The proportion of patients who achieved SVR was similar among the treatment groups: 6% (6/107) for 50 mg MMPD, 4% (5/112) for 100 mg MMPD, and 5% (5/104) for placebo (P ‫؍‬ 0.8431). Adverse-event profiles for the MMPD combination groups were similar to that for Peg-IFN-alfa and RBV alone. Nausea, arthralgia, cough, dyspnea, neutropenia, and anemia were more common in patients taking MMPD. Conclusion: The addition of MMPD to Peg-IFN-alfa-2a and RBV combination therapy did not increase the proportion of nonresponder patients with genotype 1 CHC achieving an SVR.

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991 Final Results of the Ideal (Individualized Dosing Efficacy Versus Flat Dosing to Assess Optimal Pegylated Interferon Therapy) Phase Iiib Study

Cited by 41 publications

References 0 publications

Hepatitis C comorbidities affecting the course and response to therapy

Hepatitis C comorbidities affecting the course and response to therapy

Randomized trial comparing pegylated interferon α-2b versus pegylated interferon α-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients

Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders

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