June 12, 2012

Quality of Life Undiminished by Telaprevir in Chronic Hepatitis C

By: DIANA MAHONEY, Family Practice News Digital Network

SAN DIEGO – Although the addition of telaprevir to peginterferon/ribavirin therapy for treatment of chronic hepatitis C exacerbates treatment-related side effects, the triple combination does not diminish patient quality of life relative to treatment with the peginterferon/ribavirin regimen alone, a study has shown.

In other words, adding the protease inhibitor "does not further diminish patient quality of life," lead investigator Dr. Zobair Younossi explained at the annual Digestive Disease Week. "The most important contributor to the quality of life measurement in interferon therapy is interferon itself, which is so overwhelming in terms of side effects, especially grade 4 and 5 effects, that it probably overshadows everything else," he said.


Photo courtesy US Dept. of Veterans Affairs

Adding the protease inhibitor telaprevir to the treatment for hepatitis C "does not further diminish patient quality of life," lead investigator Dr. Zobair Younossi explained at the annual Digestive Disease Week.

Studies have shown that the addition of telaprevir to standard peginterferon alfa-2a/ribavirin (PR) significantly improves treatment efficacy in treatment-naive patients with genotype 1 hepatitis C virus (HCV), but there is a perception that the additional side effect burden from adding telaprevir is prohibitive in some patients, said Dr. Younossi, chairman of the department of medicine at Inova Health System in Falls Church, Va.

Dr. Younossi and colleagues conducted post hoc analyses of data from the ADVANCE trial, in which adding telaprevir to the treatment mix significantly improved patients’ sustained virologic response compared with standard PR therapy.

In the ADVANCE study, 1,088 treatment naive HCV genotype 1 patients were assigned to one of three treatment arms: 48 weeks of standard PR therapy; 12 weeks of telaprevir plus 24 weeks PR; or 12 weeks of telaprevir plus 48 weeks of PR. Nearly 80% of patients in both telaprevir groups achieved sustained virologic response, compared with 46% of patients in the standard PR treatment group (N. Engl. J. Med. 2011;364:2405-16).

In terms of side effects, "across all phase III studies, the incidence of rash and anemia (which are the effects we’re talking about with the protease inhibitors) was 56% and 34%, respectively, among telaprevir-treated patients, and 36% and 17% in patients receiving standard treatment," Dr. Younossi said.

To assess whether and to what degree these increases played a role in patient quality of life, Dr. Younossi and colleagues analyzed the results of EQ-5D quality of life questionnaires completed at baseline and at weeks 4, 12, 24, 36, 48, and 72 by 722 patients. They derived a summary index by calculating the percentages of patients reporting problems for each of the five health-related quality of life dimensions measured (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression).

After adjustment for age and sex, the baseline mean index values for the EQ-5D were 0.92 for the telaprevir plus 24-week PR group, 0.90 for the telaprevir plus 48-week PR group, and 0.91 for the 48-week PR-only group. The percentages of patients reporting any problems in each of the five qualitative dimensions at baseline were 8.2% for mobility, 2.0% for self-care, 12.9% for usual activities, 25.7% for pain/discomfort, and 25.6% for anxiety/depression, he said.

Across all the treatment groups, the EQ-5D index scores worsened during the first 12 weeks of treatment initiation. Specifically, mean values were 0.80 for the pooled-telaprevir groups and 0.83 for the PR-only group, according to Dr. Younossi.

Also, the respective percentages of patients in the pooled-telaprevir and PR-only groups reporting any problems at week 12 were 56% and 50% for usual activities, 51% and 42% for anxiety/depression, and 60% and 63% for pain/discomfort, he said. Change from baseline in terms of reported impact on mobility and self-care were small and not reported.

At week 48, the corresponding mean EQ-5D values were 0.93 for the telaprevir plus 24-week PR group, 0.83 for the telaprevir plus 48-week PR group, and 0.84 for the PR-only group.

By week 72 the EQ-5D index values returned to baseline levels, Dr. Younossi said.

Adjusted for age and sex, the mean EQ-5D index at week 72 was higher among the patients achieving sustained virologic response (SVR) compared with those who did not, with respective values of 0.90 and 0.86. "The 4% difference is within the range of published values for the minimal clinically important difference for the EQ-5D," he said.

Furthermore, at week 72, there were fewer patients among those who experienced SVR and reported problems in each dimension, compared with those who did not experience SVR.

At week 72, after adjustment for the index at baseline, patient age, sex, race, advanced liver disease, self-reported comorbidities, and the number of adverse events during treatment, only SVR was a positive predictor of the EQ-5D index. "We saw that [SVR] was a statistically significant and meaningful predictor of health-related quality of life," he said.

The study findings are consistent with the published research on the impacts of interferon-based regimens on health-related quality of life in this patient population, "and support the value of shorter treatment duration and [SVR] from a patient-reported outcomes perspective," said Dr. Younossi.

"We certainly cannot say that adding telaprevir causes fewer side effects. It’s clear there are more side effects, but it appears that the most troublesome side effects are related to the interferon therapy," he explained. When considered in the context of the improved SVR, "the burden of the increased incidence of anemia and rash associated with telaprevir, of which few cases are severe, appears to be outweighed by the overall treatment response."

This study was sponsored by Vertex. Dr. Younossi disclosed relationships with Biolex, Vertex, Salix, GlaxoSmithKline, and Tibotec.


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