- Category: HCV Treatment
- Published on Thursday, 15 September 2011 00:00
- Written by Liz Highleyman
Adding the hepatitis C virus (HCV) protease inhibitor telaprevir (Incivek) to pegylated interferon plus ribavirin increases the chances of sustained response and many patients achieved a cure with a shorter course of therapy, researchers reported in the September 15, 2011, New England Journal of Medicine.
Kenneth Sherman and fellow investigators with the ILLUMINATE Study Team conducted a non-inferiority trial to compare rates of sustained virological response (SVR) -- or continued undetectable HCV RNA 24 weeks after completion of therapy -- for 2 treatment durations among previously untreated patients with HCV genotype 1.
People with hard-to-treat genotype 1 often need a full 48 weeks of pegylated interferon/ribavirin to achieve SVR, and even then about half do not attain a cure, the study authors noted as background.
The researchers enrolled 540 treatment-naive genotype 1 chronic hepatitis C patients. All participants first received telaprevir at a dose of 750 mg every 8 hours, 180 mcg/week pegylated interferon alfa-2a (Pegasys), and 1000-1200 mg/day weight-adjusted ribavirin for 12 weeks (T12PR12).
Participants then stopped telaprevir and continued on pegylated interferon/ribavirin alone. Patients who had an extended rapid virological response (eRVR, undetectable HCV RNA at weeks 4 and 12) were randomly assigned at week 20 to receive continued pegylated interferon/ribavirin for either 4 more weeks (T12PR24) or 28 more weeks (T12PR48). The former group, therefore, was treated for a total of 24 weeks, while the latter received the standard duration of 48 weeks.
- Overall, 352 out of 540 patients, or 65%, experienced extended rapid virological response.
- The overall sustained virological response rate was 72%.
322 patients with extended RVR were randomly assigned to the continued treatment arms:
- 149 out of 162 people (92%) in the T12PR24 group achieved SVR;
- 140 out of 169 people (88%) in the T12PR48 group achieved SVR.
- The difference of 4% fell well within the pre-set margin of 10.5%, indicating that the shorter treatment course was non-inferior to the longer duration.
- 64% of patients without extended RVR who were assigned to the longer duration arm achieved SVR.
- Adverse events included rash (37% of patients, 5% severe) and anemia (39% of patients, 6% severe).
- 18% of participants overall discontinued study drugs due to adverse events, with a higher rate among those randomized to the longer duration arm (1% in T12PR24 vs 12% in T12PR48).
- Follow-up of patients without sustained virological response showed that 55% of people who originally had resistant HCV no longer had resistant variants at their final visit (median follow-up 43 weeks).
"We found that a 24-week treatment regimen of peginterferon-ribavirin, with telaprevir added for the first 12 weeks, was noninferior to a 48-week regimen of peginterferon-ribavirin, with telaprevir added for the first 12 weeks in patients with chronic infection with HCV genotype 1 who have not received treatment previously and who had an extended rapid virologic response," the study authors concluded.
"Nearly two thirds of the enrolled patients met this definition and were eligible for an abbreviated course of therapy," they continued. "Thus, this study supports the concept of response-guided therapy. Relapse rates were low and were not significantly different between the 24-week group and the 48-week group."
Investigator affiliations: Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati , OH; Division of Hepatology, Northwestern University Medical School, Chicago, IL: Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, MA: Section of Hepatology, University of Florida, Gainesville, FL; Viral Hepatitis Center, Johns Hopkins University School of Medicine, Baltimore, MD; Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine Denver, Aurora, CO; UNC Liver Center, University of North Carolina, Chapel Hill, NC; Department of Gastroenterology and Hepatopancreatology, Erasme Hospital Brussels, Brussels, Belgium; Department of Hepatology, Academic Medical Center of the University of Amsterdam, Amsterdam, Netherlands; Vertex Pharmaceuticals, Cambridge, MA; Department of Medicine, Cedars–Sinai Medical Center, Los Angeles, CA.
KE Sherman, SL Flamm, NH Afdhal, et al. Response-Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection. New England Journal of Medicine 365(11):1014-1024 (abstract). September 15, 2011.
Vertex Pharmaceuticals. New England Journal of MedicinePublishes Data from Phase 3 ILLUMINATE Study of Incivek (telaprevir) in Hepatitis C. Press release. September 14, 2011.