Extending peginterferon/ribavirin therapy from 24 to 48 weeks does not benefit most genotype 1 hepatitis C patients who achieve an extended rapid viral response to a telaprevir-based combination protocol, according to results from an open-label, randomized trial reported in the Sept. 15 issue of the New England Journal of Medicine.
The telaprevir-based regimen in the phase III Illuminate (Illustrating the Effects of Combination Therapy with Telaprevir) trial consisted of 750 mg of telaprevir every 8 hours, 180 mcg of peginterferon alfa-2a per week, and 1,000-1,200 mg of ribavirin per day for 12 weeks, followed by peginterferon/ribavirin. Those treatment-naive patients who had a rapid response to the telaprevir-based regimen were randomized, after week 20, to receive the dual therapy for either 4 more weeks or 28 more weeks. Rapid response was based on undetectable RNA levels of the hepatitis C virus (HCV) at weeks 4 and 12.
Patients who had not achieved an extended rapid viral response (eRVR) were assigned to the 48-week protocol, according to Dr. Kenneth Sherman of the University of Cincinnati College of Medicine and his colleagues.
In all, 540 patients were initially treated with the 12-week telaprevir regimen described above, and 352 patients achieved eRVR. Of these, 322 remained on treatment and 162 were randomized to the 24-week protocol and 160 were randomized to the 48-week treatment arm, they wrote (N. Engl. J. Med. 2011:365: 1014-24).
The overall rate of sustained virologic response (SVR) in the full study population was 72%, while the rates in the patients who achieved eRVR were 92% in the 24-week group and 88% in the 48-week group, the investigators reported.
Of the 118 patients who had not achieved eRVR in the initial trial and who were assigned to the 48-week protocol and the 100 patients who discontinued treatment before week 20, 76 (64%) and 23 (23%) of patients, respectively, achieved an SVR, they wrote.
More patients in the shorter-treatment group completed the treatment compared with the longer-treatment group (99% vs. 74%).
The relapse rate post treatment was 8% in the overall group, and it was 6% and 3%, respectively, in the 24- and 48-week groups. "The HCV RNA level was undetectable at 72 weeks after the start of treatment in 70% of patients overall," the authors reported, with an absolute difference of –0.5 percentage points between the 24-week (85%) and the 48-week (85.5%) groups.
There were more serious adverse events, most commonly anemia, in the longer-duration group than in the shorter, and there were more adverse event–related treatment discontinuations in the longer-duration group as well, the authors wrote. Specifically, 2% of patients in the 24-week group and 10% of those in the 48-week-group who had an eRVR experienced serious adverse events.
Eighteen percent of the patients overall, and 1% and 12% of the 24-week and 48-week groups, respectively, discontinued all of the study drugs because of adverse events, which included fatigue, pruritus, nausea, anemia, headache, rash, insomnia, diarrhea, and flulike illness, they reported.
Importantly, this response-guided treatment regimen "resulted in a shorter treatment duration with high rates of sustained virologic response for approximately two-thirds of treated patients," the authors stressed. Further, "the treatment regimen was highly effective in patients with a historically poor treatment response, including blacks, patients with bridging fibrosis or cirrhosis, and patients with high HCV RNA levels." The shorter treatment strategy appears to decrease the risk of exposure to potential side effects from telaprevir, an oral HCV protease inhibitor, as well as the adverse events associated with the 48-week peginterferon and ribavirin regimen.
The Illuminate study was supported by Vertex Pharmaceuticals and Tibotec. The authors disclosed relationships with numerous pharmaceutical companies, including Vertex, which manufactures telaprevir, and Tibotec, which was involved in the drug’s development.