Response-guided telaprevir combination treatment for hepatitis C virus infection
Kenneth E Sherman, Steven L Flamm, Nezam H Afdhal, David R Nelson, Mark S Sulkowski, Gregory T Everson, Michael W Fried, Michael Adler, Hendrik W Reesink, Marie Martin, Abdul J Sankoh, Nathalie Adda, Robert S Kauffman, Shelley George, Christopher I Wright, Fred Poordad, ILLUMINATE Study Team, M Adler, Jean Delwaide, Y Horsmans, H van Vlierberghe, H W Reesink, C Richter, N Afdhal, V Araya, S Arora, L Balart, M Bennett, B Berk, D Bernstein, J Bloomer, R Brown Jr, N Bzowej, R Chasen, J Cochran, J Crippin, G Davis, M Davis, E DeJesus, A Di Bisceglie, D Dieterich, S Esposito, G Everson, S L Flamm, J Franco, B Freilich, M W Fried, R Ghalib, E Godofsky, S Gordon, C Howell, W Hutson, I Jacobson, M Jonas, B Kaufman, P Kwo, E Lawitz, M Lucey, M Lyons, P Martin, A Muir, K Mullen, D Nelson, T Nguyen, P Pockros, F F Poordad, R Reindollar, J Reinus, M Rodriguez-Torres, L Rossaro, R Rubin, R Satyanarayana, J Scott, T Sepe, N Shah, A Sheikh, M Sheikh, A Sherker, K E Sherman, J Strohecker, M Sulkowski, G Szabo, N Terrault, H Tobias, N Tsai, H Vargas, K Workowski, G Wu, R Yapp, Z Younes, Z Younossi, A Zaman, Kenneth E Sherman, Steven L Flamm, Nezam H Afdhal, David R Nelson, Mark S Sulkowski, Gregory T Everson, Michael W Fried, Michael Adler, Hendrik W Reesink, Marie Martin, Abdul J Sankoh, Nathalie Adda, Robert S Kauffman, Shelley George, Christopher I Wright, Fred Poordad, ILLUMINATE Study Team, M Adler, Jean Delwaide, Y Horsmans, H van Vlierberghe, H W Reesink, C Richter, N Afdhal, V Araya, S Arora, L Balart, M Bennett, B Berk, D Bernstein, J Bloomer, R Brown Jr, N Bzowej, R Chasen, J Cochran, J Crippin, G Davis, M Davis, E DeJesus, A Di Bisceglie, D Dieterich, S Esposito, G Everson, S L Flamm, J Franco, B Freilich, M W Fried, R Ghalib, E Godofsky, S Gordon, C Howell, W Hutson, I Jacobson, M Jonas, B Kaufman, P Kwo, E Lawitz, M Lucey, M Lyons, P Martin, A Muir, K Mullen, D Nelson, T Nguyen, P Pockros, F F Poordad, R Reindollar, J Reinus, M Rodriguez-Torres, L Rossaro, R Rubin, R Satyanarayana, J Scott, T Sepe, N Shah, A Sheikh, M Sheikh, A Sherker, K E Sherman, J Strohecker, M Sulkowski, G Szabo, N Terrault, H Tobias, N Tsai, H Vargas, K Workowski, G Wu, R Yapp, Z Younes, Z Younossi, A Zaman
Abstract
Background: Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon-ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, -10.5%) to compare rates of sustained virologic response among patients receiving two treatment durations.
Methods: We enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment. All patients received telaprevir at a dose of 750 mg every 8 hours, peginterferon alfa-2a at a dose of 180 μg per week, and ribavirin at a dose of 1000 to 1200 mg per day, for 12 weeks (T12PR12), followed by peginterferon-ribavirin. Patients who had an extended rapid virologic response (undetectable HCV RNA levels at weeks 4 and 12) were randomly assigned after week 20 to receive the dual therapy for 4 more weeks (T12PR24) or 28 more weeks (T12PR48). Patients without an extended rapid virologic response were assigned to T12PR48.
Results: Of the 540 patients, a total of 352 (65%) had an extended rapid virologic response. The overall rate of sustained virologic response was 72%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 149 (92%) in the T12PR24 group and 140 (88%) in the T12PR48 group had a sustained virologic response (absolute difference, 4 percentage points; 95% confidence interval, -2 to 11), establishing noninferiority. Adverse events included rash (in 37% of patients, severe in 5%) and anemia (in 39%, severe in 6%). Discontinuation of all the study drugs was based on adverse events in 18% of patients overall, as well as in 1% of patients (all of whom were randomly assigned) in the T12PR24 group and 12% of the patients randomly assigned to the T12PR48 group (P<0.001).
Conclusions: In this study, among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon-ribavirin for 24 weeks, with telaprevir for the first 12 weeks, was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12, with an extended rapid virologic response achieved in nearly two thirds of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ILLUMINATE ClinicalTrials.gov number, NCT00758043.).
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Source: PubMed