Clinical

Shorter treatment effective for some hepatitis C patients

Last Updated: 2011-09-14 18:00:08 -0400 (Reuters Health)

By Gene Emery

NEW YORK (Reuters Health) - Giving peginterferon-ribavirin therapy for just 24 weeks once combination treatment with telaprevir is complete can be just as effective as a 48-week regimen for curing chronic hepatitis C infection.

But reducing the duration, which cuts back on side effects, only works in patients who responded rapidly to the initial stage of the therapy, researchers reported online today in the New England Journal of Medicine.

"In our study about two thirds of patients -- 65% -- were eligible for the shorter therapy based on their extended rapid viral response. They could have given up 24 weeks of peginterferon-ribavirin therapy," study leader Dr. Kenneth Sherman of the University of Cincinnati College of Medicine told Reuters Health in a phone interview.

"This does represent a new standard," he said.

The noninferiority study was designed to make sure patients with undetectable HCV RNA at weeks four and 12 don't do worse with a shorter course of peginterferon-ribavirin therapy when telaprevir was initially part of the mix.

With shorter-duration treatment, "it's logical that costs will be lower," said Dr. Sherman, who emphasized that the researchers did not do a formal cost analysis.

Vertex Pharmaceuticals, which sells telaprevir under the brand name Incivek, and Tibotec, which has rights to market the drug in many countries outside North America, paid for the ILLUMINATE study. Telaprevir was approved by the U.S. Food and Drug Administration in May.

The study began by screening volunteers from Belgium, the Netherlands and the United States with HCV genotype 1. None had previously received treatment.

Five hundred forty were assigned to receive 12 weeks of therapy with telaprevir (at 750 mg every 8 hours), peginterferon alfa-2a (180 mcg per week) and ribavirin (1,000 to 1,200 mg per day), with the peginterferon-ribavirin combination given for an additional 12 weeks.

One hundred patients dropped out of the initial treatment phase (including 12 who withdrew for virologic failure, 62 because of side effects, and 12 because they refused further treatment or withdrew consent).

Of the 440 who remained, 322 had an extended rapid virologic response, that is, HCV RNA was still undetectable in their blood at 20 weeks. They were randomly assigned to either stop treatment at the end of the 24 weeks, or continue for another 24 weeks.

Of the 162 with an extended rapid virologic response who stopped at 24 weeks, 92% remained virus free at 48 weeks.

Among the remaining 160, who stayed on peginterferon-ribavirin therapy for another 24 weeks, 88% had a sustained virologic response at 48 weeks. In that group, 41 opted out of the final 24 weeks of therapy (20 due to adverse effects and 6 for virologic failure).

By comparison, of the 118 patients who did not have an extended rapid response and got 24 more weeks of therapy, 64% had a sustained virologic response. Thirty nine of those discontinued treatment -- 12 because of side effects and 18 due to virologic failure.

In all, 72% had a rapid response to the three-drug regimen by the fourth week; by the 12-week mark, 65% were still showing no trace of the virus. (To put those success rates into perspective, 48 weeks of therapy with peginterferon and ribavirin, but not telaprevir, typically produces a sustained response in 40% to 50% of cases.)

Overall, in the ILLUMINATE study, 18% of the volunteers were taken off the treatment because of side effects. It produced some form of anemia in 39% of patients (it was severe in 6% of cases, and 32 patients needed blood transfusions). Rash occurred in 37% (severe in 5%). Most of the rashes occurred during the first eight weeks of treatment.

"The three-drug regimen increases the risk of anemia, but the good news is that because the three drugs were only given together for 12 weeks, that's not a long-term problem in the majority of patients," Dr. Sherman said.

Serious side effects were more common in the group that got the full 48 weeks of peginterferon-ribavirin therapy. The rate was 10% compared to 2% among patients whose treatment time was reduced (P=0.005).

"Fatigue was the most common adverse event (68%), followed by pruritus (51%), nausea (47%), anemia (39%), headache (38%), rash (37%), insomnia (32%), diarrhea (28%), and influenza-like illness (26%)," the researchers reported.

Conventional therapy with 48 weeks of peginterferon and ribavirin is said to cost roughly $30,000, Dr. Sherman said. But telaprevir costs much more. "The numbers I've seen quoted are $49,000 wholesale."

"While that sounds like of money for a short course of treatment, that needs to be balanced against the societal costs of untreated hepatitis C, where even a single liver transplant could be valued at hundreds of thousands of dollars, not to mention the associated medical costs leading up transplantation," he said.

Dr. Sherman said some patients responded so well and so quickly, "I'm confident that there were patients where we probably could have shortened treatment even more." But formal tests will be needed to show if that would be safe and effective.

SOURCE: http://bit.ly/pbc5vb

N Engl J Med 2011; 365:1014-1024.