Major Finding: Of 161 treatment-naive patients, 109 had undetectable plasma levels of HCV RNA at weeks 4-20 and stopped treatment at 24 weeks (96% sustained virologic response), 29 patients with detectable HCV RNA continued the standard 48 weeks of treatment (79% sustained virologic response), and 33 patients dropped out.
Data Source: A multicenter, phase II, open-label study of telaprevir with ribavirin and peginterferon alfa-2a or 2b in treatment-naive patients aged 18-65 years with no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use.
Disclosures: The trial was funded by Tibotec, a division of Janssen-Cilag, and by Vertex Pharmaceuticals. The authors reported ties to 18 pharmaceutical and biomedical technology companies.
In patients who have chronic hepatitis C, combining telaprevir with ribavirin and peginterferon alfa-2a or 2b yielded sustained virologic response rates of more than 80%, regardless of which type of interferon or which dosing regimen of telaprevir was used, Dr. Patrick Marcellin and his colleagues reported.
The researchers assessed the efficacy and safety of four different dosing approaches in a phase II, open-label clinical trial, which they described as “the first trial comparing the two licensed peginterferon alfa/ribavirin treatments in combination with the same protease inhibitor.”
The study was conducted at 30 medical centers in Austria, Belgium, France, Germany, Italy, the Netherlands, and Spain, and included treatment-naive patients aged 18-65 years who had no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use (Gastroenterology 2011;140:459-68.e1).
The 161 study subjects were randomly assigned to four treatment groups: 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2a and ribavirin; 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2b and ribavirin; 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2a and ribavirin; or 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2b and ribavirin, said Dr. Marcellin, who is with Beaujon Hospital, University of Paris, Clichy, France, and his associates.
Subjects who had undetectable plasma levels of hepatitis C virus (HCV) RNA at weeks 4-20 (109 patients) were scheduled to discontinue treatment at 24 weeks, while those who still had detectable HCV RNA (29 patients) were scheduled to continue for the standard 48 weeks of treatment. A total of 33 patients dropped out of the study before completing their assigned treatment.
The main efficacy end point was the percentage of patients who achieved a sustained virologic response, with levels of HCV RNA that were either undetectable or less than 25 IU/mL.
Overall, this percentage was not significantly different among the four treatment groups: 85% in group 1, 81% in group 2, 83% in group 3, and 82% in group 4.
Given the small number of patients in each treatment arm of this trial, different dosing regimens warrant further study in a larger clinical trial, Dr. Marcellin and his associates added.
This primary outcome also was not significantly different when the results were pooled for all patients taking telaprevir every 8 hours (83%) compared with all patients taking telaprevir every 12 hours (82%), as well as when the results were pooled for all patients taking peginterferon alfa-2a (84%) compared with all patients taking peginterferon alfa-2b (82%).
When the results were assessed according to duration of treatment, 96% of the patients who were treated for only 24 weeks achieved a sustained virologic response, as did 79% of those who received the standard 48-week course, the investigators said.
This strategy of guiding treatment duration according to each patient's virologic response at 4-20 weeks was clearly successful, allowing the majority of patients to cut their course of treatment by half without adversely affecting efficacy.
“This response-guided treatment duration strategy is currently being further explored in ongoing telaprevir phase III clinical trials in treatment-naive patients,” Dr. Marcellin and his colleagues noted.
When the results were assessed according to completion of assigned treatment, 95% of the 128 patients who completed treatment achieved a sustained virologic response.
Both the every-8-hours and every-12-hours doses of telaprevir were equally effective at producing a sustained virologic response, and were equally tolerated by patients. There also were no significant differences between the two doses in relapse rates or in safety profiles. “Thus, it could be hypothesized that coadministration of telaprevir with standard therapy might allow for less frequent telaprevir dosing,” the investigators said.
Similarly, both formulations of peginterferon were equally effective in this study, although the two agents have different pharmacokinetic properties and a recent meta-analysis suggested that peginterferon alfa-2a is slightly more effective.