BOSTON - A hepatitis C treatment regimen of sofosbuvir and ledipasvir without ribavirin is associated with significant improvement in patient-reported outcomes, new research suggests.
“This is really the first time in the history of hepatitis C that we can show improvement of [patient reported outcomes (PROs)] during treatment because all the other treatments [that contain ribavirin] show some decline,” Dr. Zobair Younossi said at the annual meeting of the American Association for the Study of Liver Diseases.
The improvement in PROs occurs as early as 2 weeks after the initiation of therapy, and increased by up to 7.4% in 8 weeks, 7% in 12 weeks, and 6.7% in 24 weeks in patients not receiving ribavirin, according to Dr. Younossi, chair of medicine and executive director of the Center for Liver Diseases at Inova Fairfax Medical Campus and vice president for research at Inova Health System in Falls Church, Va.
The investigators surveyed 1,952 patients with chronic hepatitis C virus genotype 1 who participated in the ION-1, -2, and -3 clinical trials and received sofosbuvir and ledipasvir alone or with ribavirin for either 8 weeks (n = 431), 12 weeks (n = 867), or 24 (n = 654) weeks.
PROs were assessed at baseline, weeks 2, 4, 8, and 12 during treatment, and weeks 4 and 12 post-treatment using four validated instruments: Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Short Form-36, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Work Productivity and Activity Index (WPAI).
Changes in individual domain scores were significantly higher from baseline throughout treatment for patients not receiving ribavirin on all domains, except work absenteeism, Dr. Younossi said. The overall work productivity score on the WPAI also improved significantly, by 10.3% at 8 and 12 weeks, and the activity score improved by 7.4% at 24 weeks.
Scores on the CLDQ-HCV and other PRO instruments improved during the first 2 weeks for patients in either group, but continued to rise for patients not receiving ribavirin. CLDQ-HCV scores remained significantly higher compared with baseline at 8 weeks, 12 weeks, and 14 weeks of treatment.
In contrast, CLDQ-HCV scores and other PRO scores dropped off at 2 weeks after their initial rise among patients receiving ribavirin and remained flat until treatment was discontinued. Overall work productivity on the WPAI declined by 6.3% at 12 weeks, with a further 4.9% decline noted at 24 weeks of treatment.
Patients on a ribavirin regimen also had a 6.7% decline from baseline in the mental component summary score of the SF-36. After treatment with ribavirin, PRO scores improved rapidly and were not different from the ribavirin-free arm after 12 weeks of follow-up.
Among all patients, achieving SVR-12 was shown to be associated with significant PRO improvement. This data suggests that achieving SVR-12 not only improves patient reported outcomes, but could also lead to improvements in the presenteism aspect of work productivity and thus potentially could have a positive economic impact on workers currently affected by HCV, Dr. Younossi said in an interview.
In multivariate analysis, independent predictors of PRO impairment at baseline and all time points were: older age, female gender, pretreatment depression, anxiety, insomnia, clinically overt fatigue, and type 2 diabetes mellitus. Ribavirin was a significant predictor of impairment in mental component score on the SF-36, work productivity, and activity (beta -5.4% to -8.8%).
“The AASLD/IDSA guidelines suggest that we should treat patients with very mild disease as long as they have significant fatigue, and these data support that recommendation,” he said.
During a discussion of the study, audience members questioned whether, in the absence of a placebo arm in the ION trials, the authors could conclude that the benefits observed in PROs were due to the ribavirin-free regimens and not due to virologic improvements or the psychological benefits of simply taking a medication.
Dr. Younossi said patients were unaware of their viral load during treatment and that the argument for the psychological effect of treatment on PROs has been resolved. The decline in PROs observed in patients taking ribavirin has been observed in other studies and is related to ribavirin-associated side effects. PRO results from another Gilead-sponsored ribavirin study that includes placebo are expected to be reported next year, he added.
Karen Blum contributed to this report.
This story was updated 11/11/2014.