- File Under telaprevir-incivek
By Michael Smith, North American Correspondent, MedPage Today
Published: September 14, 2011
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Response-guided therapy with the protease inhibitor telaprevir (Incivek) can cut the treatment period for hepatitis C (HCV) in half, researchers reported.
In an open-label randomized trial, 24 and 48 weeks of standard therapy – each combined with telaprevir for the first 12 weeks – had equivalent efficacy among patients who responded early and strongly, according to Kenneth Sherman, MD, PhD, of the University of Cincinnati College of Medicine, and colleagues.
But those getting the shorter therapy had significantly fewer adverse events, they reported in the Sept. 15 issue of the New England Journal of Medicine.
Note that in this study, the investigators evaluated the efficacy of shorter treatment duration to decrease the risk of exposure of patients to adverse events associated with the 48-week use of peginterferon and ribavirin.
Point out that a regimen of peginterferon–ribavirin for 24 weeks was noninferior to the same regimen for 48 weeks in patients with extended rapid virologic response, and was associated with significantly less discontinuation of all the study drugs based on adverse events.
Telaprevir was approved earlier this year to be used in combination with standard HCV therapy with pegylated interferon and ribavirin. It is one of two new medications -- the other is boceprevir (Victrelis) -- that target the virus directly, in contrast to the standard therapy, which boosts the immune system.
Both the standard therapy and telaprevir are associated with a range of adverse events that can lead patients to stop therapy, the researchers noted, so that a shorter course would have important advantages.
To test the idea, they enrolled 540 patients with genotype 1 HCV -- the most difficult to treat -- who had not previously had therapy. All patients were given the three drugs for the first 12 weeks, followed by 12 weeks of peg-interferon and ribavirin alone.
At week 24, patients who had what the researchers called an "extended rapid virologic response" were randomly assigned to stop treatment or to have another 24 weeks of peg-interferon and ribavirin.
Patients who did not have an extended rapid response – defined as undetectable HCV RNA at both weeks four and 12 of treatment – were non-randomly assigned to the longer treatment arm.
The main goal of the analysis was to see if there was a difference in the rate of sustained virologic response -- defined as undetectable HCV both at the end of treatment and 24 weeks later – among the randomized patients.
The study was designed as a non-inferiority trial, with the margin of non-inferiority set at minus 10.5%, the researchers noted.
Among the 540 patients, the overall rate of sustained virologic response was 72%.
A total of 352 patients -- 65% -- had an extended rapid virologic response, 30 dropped out before randomization, and the rest were randomly assigned to a study group. Among those randomized:
149 of 162 patients in the short arm – or 92% -- had a sustained virologic response, compared with 140 of 169 (or 88%) in the long arm. The absolute difference of four percentage points with a 95% confidence interval from minus two to 11 established non-inferiority.
Among the patients who did not have an extended rapid virologic response and were assigned to the long arm, 76 (or 64%) had a sustained virologic response.
Adverse events included rash in 37% of patients that was severe in 5% and anemia in 39% that was severe in 6%.
Overall, 18% of patients stopped all study drugs because of adverse events.
After randomization, however, only 1% of those assigned to the short arm dropped out, compared with 12% of those in the long arm, a difference that was significant at P<0.001.
The researchers concluded that the results support the notion of using early response to guide treatment duration.
The study was supported by Vertex Pharmaceuticals and Tibotec. Sherman reported financial links with Vertex, Tibotec, Merck, SciClone, GSK, Three Rivers, J&J, Regulus, Valeant, Anadys, Schering, Baxter, Astellas, Boehringer Ingelheim, UBC Healthcare, Roche /Genentech, Gilead, BMS, MedPace, and Pfizer.
Primary source: New England Journal of Medicine
Sherman KE, et al. "Response-Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection." N Engl J Med 2011; 365:1014-1024.