Clinical

Hep C retreatment with interferon may be unwise: study

Last Updated: 2013-02-08 10:07:28 -0400 (Reuters Health)

By David Douglas

NEW YORK (Reuters Health) - Patients with hepatitis C and chronic liver disease who fail to respond or who relapse on interferon monotherapy are not helped by retreatment, according to a review of trials.

In an email to Reuters Health, Dr. Ronald L. Koretz cited three observations from the analyses. First, he said, "there were no clinically meaningful benefits found from treating patients." Second, "the low risk of bias trials showed that those given pegylated interferon, versus no treatment, had a higher mortality."

Finally, surrogate markers may have obscured actual outcomes. "In spite of the failure to see any clinical benefit (and perhaps even seeing harm), the treatment did improve the surrogate outcomes of sustained viral response (SVR) and markers of inflammation," Dr. Koretz said.

In a review online January 13 in The Cochrane Library, Dr. Koretz of Granada Hills, California and colleagues note that SVR and other surrogate outcomes are widely accepted but have not been validated.

Altogether the team examined data from seven trials with 1,976 patients. Two of the trials, with 1,676 patients, were considered to have a low risk of bias.

Dr. Koretz admits that the review assessed interferon monotherapy, which is hardly ever used anymore. However, he noted, "interferon is part of current combination therapy."

Results from four trials showed significantly higher SVR rates with interferon (3.6% vs 0.2%), and two trials showed improvements in fibrosis and inflammation, as reflected by a significant improvement in METAVIR activity score (by 65.0% vs 43.5%). Three showed less variceal bleeding (0.5% vs 2.1%). No significant differences were seen with regard to histologic fibrosis assessments.

Among other findings were that adverse effects tended to be more common in interferon recipients, and the one trial that reported on quality of life showed significantly greater pain in interferon recipients.

Overall, the risk of death was no higher for interferon than for placebo or no treatment. However, in the low bias risk trials, the risk of death was significantly higher with interferon (9.4%) than with placebo or no treatment (6.7%).

"Based on these results," Dr. Koretz said in a statement, "interferon monotherapy cannot be recommended for chronic hepatitis C patients who have already failed one course of treatment and are being retreated. Furthermore, patients who are receiving interferon as part of a combination therapy should be informed about this potential adverse effect."

In his remarks to Reuters Health, Dr. Koretz stressed, "I use the word 'potential' because we were not able to demonstrate that this was not a type I error."

He added, "Sustained viral response did not suggest that a patient who was destined to develop symptoms or death from hepatitis C was cured, at least in this setting. This tells us that as a treatment outcome it is not universally reliable and needs to be validated before it can be viewed as the goal of any therapy in other clinical scenarios."

This finding, he continued, "has relevance to any treatment program that is proposed for hepatitis C, even programs that do not employ interferon, namely that the surrogate outcomes failed validation in this scenario and cannot be assumed to be valid in others (so they do need to be validated before we can be sure that they can be used)."

SOURCE: http://bit.ly/YDUGk3

Cochrane Database of Systematic Reviews 2013.