Longer HCV Treatment Outperforms Short Course

RICHMOND, Va., July 11 -- Longer is better when it comes to treatment for hepatitis C, researchers here said.
In an industry-sponsored clinical trial, outcomes were significantly inferior when patients were treated with pegylated interferon alfa-2a (Pegasys) and ribavirin (Copegus) for 16 weeks instead of the standard 24, according to a report in the July 12 issue of the New England Journal of Medicine.
The finding supports current recommendations that patients with hepatitis C genotypes two or three should be treated for 24 weeks, said Mitchell Shiffman, M.D., of Virginia Commonwealth University Medical Center, and colleagues.
About 80% of patients with those genotypes who are treated for 24 weeks have a sustained virologic response - defined as less than 50 IU of hepatitis RNA per mL of serum 24 weeks after the end of treatment. (Patients with genotype one require 48 weeks of therapy.)
But small, randomized trials had suggested that shortening the treatment period could provide much the same benefit at lower cost and with fewer adverse events, the researchers noted. (See Short-Course Treatment Effective In Chronic HCV)
To help settle the issue, the researchers randomized 1,469 patients with hepatitis C genotypes two or three to receive 180 micrograms of peginterferon alfa-2a weekly and 800 milligrams of ribavirin daily for either 16 or 24 weeks.
The 16-week course of treatment was significantly inferior, the researchers found:
Sustained virologic response - the primary endpoint - was 62% in the 16-week group and 70% in the 24-week group.
The odds ratio for a sustained response was 0.67, with a 95% confidence interval from 0.54 to 0.84, which was significant at P<0.001.
The relapse rate - defined as detectable hepatitis RNA during follow-up in patients who had undetectable levels at the end of treatment -- was 31% in the 16-week group and 18% in the 24-week group, which was significant at P<0.001.
In patients with a low pre-treatment viral level (400,000 IU per milliliter or less), the sustained virologic response rate was 82% in the 16-week group and 81% in the 24-week group.
Among patients who responded quickly (with undetectable hepatitis by the fourth week) the sustained virologic response rates were 79% in the 16-week group and 85% in the 24-week group, a difference that was significant at P=0.02.
Interestingly, at the end of treatment, patients in the 16-week group were almost twice as likely as those in the other arm to have undetectable serum levels of hepatitis RNA, the researchers found, because more patients in the 24-week group withdrew early and were considered not to have had a response.
In other words, the difference in sustained virologic response is caused almost entirely by the increased relapse rate in the 16-week group, the researchers said.
Adverse events were similar between the arms, the researchers said.
Low initial viral load and rapid initial response predicted a better outcome, the researchers said, so shorter treatment duration might be possible in such patients.
In general, however, "these patients should not be routinely treated for less than the currently recommended 24 weeks," they concluded.
While the findings appear stark and clear, the take-home message may be "more complicated than the findings of the current study suggest," according to T. Jake Liang, M.D., of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md.
In fact, Dr. Liang said in an accompanying editorial, some of the detailed results of the study suggest a one-size-fits-all approach may be less effective than tailoring treatment to the individual.
For example, he said, the study's findings suggest that "patients with [hepatitis] genotype three, high viral load, advanced fibrosis, and obesity who are black, older, and male should be treated for 24 weeks."
In contrast, he said, whites with genotype two and the opposite characteristics could get a good outcome after 16 weeks.
As the state of knowledge increases, he said, it should be possible to construct "a customized management and therapeutic regimen" for each patient.
The study was supported by Roche. Dr. Shiffman reports financial links with Roche, Schering-Plough, Vertex Pharmaceuticals, Valeant, Coley Pharmaceuticals, Gilead Sciences, and GlaxoSmithKline. Other investigators report financial links with Roche, Schering-Plough, Coley Pharmaceuticals, Intermune, Valeant, Gilead, GlaxoSmithKline, and Human Genome Sciences. Two authors, Amy Lin, M.S., and Ash Soman, M.B.B.S, are employees of Roche. Primary source: New England Journal of MedicineSource reference: Shiffman ML et al. "Peginterferon Alfa-2a and Ribavirin for 16 or 24 Weeks in HCV Genotype 2 or 3." N Engl J Med 2007;357:124-34. Additional source: New England Journal of MedicineSource reference: T. Jake Liang "Shortened Therapy for Hepatitis C Virus Genotype 2 or 3 - Is Less More?" N Engl J Med 2007;357:176-78.