Donald M. Jensen, MD; Patrick Marcellin, MD; Bradley Freilich, MD; Pietro Andreone, MD; Adrian Di Bisceglie, MD; Carlos E. Brandão-Mello, MD, PhD; K. Rajender Reddy, MD; Antonio Craxi, MD; Antonio Olveira Martin, MD; Gerlinde Teuber, MD; Diethelm Messinger, MS; James A. Thommes, MD; Andreas Tietz, MD
Many patients with chronic hepatitis C have not responded to therapy with pegylated interferon plus ribavirin.
To evaluate use of peginterferon-Î±2a plus ribavirin to re-treat nonresponders to peginterferon-Î±2b plus ribavirin.
Randomized, parallel-group trial conducted between September 2003 and February 2007. Patients and researchers were not blinded to intervention assignment. Random assignment was centralized, computer-generated, and stratified by geographic region, hepatitis C virus (HCV) genotype, and histologic diagnosis.
106 international centers.
950 nonresponders to 12 or more weeks of therapy with peginterferon-Î±2b plus ribavirin.
Peginterferon-Î±2a, 360 Âµg/wk, for 12 weeks, then 180 Âµg/wk to complete 72 weeks (group A) or 48 weeks (group B), or peginterferon-Î±2a, 180 Âµg/wk for 72 weeks (group C) or 48 weeks (group D). All patients received ribavirin, 1000 or 1200 mg/d.
Sustained virologic response (SVR), defined as undetectable (<50 IU/mL) HCV RNA levels 24 weeks after the end of treatment.
The SVR rates in groups A (nÂ = 317), B (nÂ = 156), C (nÂ = 156), and D (nÂ = 313) were 16%, 7%, 14%, and 9%, respectively (relative risk [RR] for group A vs. group D [the primary comparison], 1.80 [95% CI, 1.17 to 2.77]; PÂ = 0.006). Extended treatment duration increased SVR rates (16% for 72 weeks [groups A and C] vs. 8% for 48 weeks [groups B and D]; RR, 2.00 [CI, 1.32 to 3.02]; PÂ < 0.001). Complete viral suppression (HCV RNA level <50 IU/mL)at week 12 was achieved in 21% of patients in groups A and B and 13% of those in groups C and D. Rates of SVR were 49% (77 of 157 patients) and 4% (32 of 719 patients) among those with and without complete viral suppression at week 12, respectively.
Nonresponders to peginterferon-Î±2a plus ribavirin were not evaluated.
Re-treating nonresponders to therapy with peginterferon-Î±2b plus ribavirin for 72 weeks significantly increases SVR rates compared with re-treating them for 48 weeks. The overall SVR rate was low, but patients who are most likely to respond to re-treatment can be identified at week 12.
Jensen DM, Marcellin P, Freilich B, Andreone P, Di Bisceglie A, Brandão-Mello CE, et al. Re-treatment of Patients With Chronic Hepatitis C Who Do Not Respond to Peginterferon-α2b: A Randomized Trial. Ann Intern Med. ;150:528–540. doi: 10.7326/0003-4819-150-8-200904210-00007
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Published: Ann Intern Med. 2009;150(8):528-540.
Gastroenterology/Hepatology, Infectious Disease, Liver Disease.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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