Lower-Dose Therapy Controls HCV

Lower-Dose Therapy Controls HCV

By Charles Bankhead, Staff Writer, MedPage Today
Published: August 05, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit
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Action Points
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■Explain to patients that in this study a low-dose antiviral therapy for hepatitis C infection proved as effective as standard-dose therapy.
Hepatitis C (HCV) therapy based on low-dose peginterferon alpha-2b (Peg-Intron) achieved a sustained virologic response rate and tolerability comparable to a higher dose of alpha-2b and peginterferon alpha-2a (Pegasys), a multicenter clinical trial found.

Rates of sustained virologic response ranged from 38% to 41% among the three regimens. Relapse rates were similar among the three treatment groups, and serious adverse events occurred in 9% to 12% of patients in each group.

The findings came as a surprise, given evidence of a higher rate of sustained response in patients treated with standard-dose peginterferon alpha-2b.

"We aimed to test the hypothesis that use of standard-dose peginterferon alpha-2b with ribavirin would result in a higher rate of sustained virologic response than with the low-dose regimen," John G. McHutchison, MD, of Duke University in Durham, N.C., and colleagues reported in the Aug. 6 New England Journal of Medicine.

"Although our data do not support this hypothesis, a significant interaction between treatment group and sex suggests that women may have higher rates of sustained virologic response with standard-dose than with low-dose peginterferon alpha-2b."

Treatment guidelines for hepatitis C infection recommend peginterferon alpha-2a or alpha-2b in combination with ribavirin. However, comparative data on the two therapies have been scant.

In an effort to clarify their relative effectiveness and safety, investigators at 118 sites in the U.S. randomized 3,070 patients with HCV genotype 1 to one of three treatment groups:

•peginterferon alpha-2b at a standard dose of 1.5mcg/kg/week plus ribavirin 800 to 1400 mg/d
•peginterferon alpha-2b at a low dose of 1.0 mcg/kg/week plus ribavirin 800 to 1400 mg/d
•peginterferon alpha-2a at a dose of 180 mcg/week plus ribavirin 1000 to 1200 mg/d

Randomized treatment continued for a maximum of 48 weeks, and patients were followed for an additional 24 weeks.

The primary endpoint was sustained virologic response, defined as undetectable HCV RNA 24 weeks after completion of therapy.

When the study ended, rates of sustained virologic response were 38% with low-dose peginterferon alpha-2b, 39.8% with standard-dose alpha-2b, and 40.9% with peginterferon alpha-2a.

Relapse rates were 20% with low-dose peginterferon alpha-2b, 23.5% with standard-dose alpha-2b, and 31.5% for peginterferon alfa-2a.

Overall, patients who had undetectable HCV RNA levels after four and 12 weeks of treatment had sustained virologic response rates of 86.2% and 78.7%, respectively.

Higher ribavirin doses were associated with an increased likelihood of sustained virologic response in all three treatment groups, the authors said.

Patients who weighed 75 to 85 kg received 1000 mg of ribavirin if they were randomized to peginterferon alpha-2b and 1200 mg if they received peginterferon alpha-2a.

In these heavier patients, the sustained response rate was about 10 percentage points higher in the peginterferon alpha-2a group, suggesting that larger patients treated with peginterferon alpha-2b also should receive the higher dose of ribavirin.

Although the overall results did not support the superiority of standard-dose peginterferon alpha-2b, female patients in the standard-dose group had a sustained virologic response rate of 44.3% compared with 35.9% in the low-dose alpha-2b group.

The authors found a significant interaction between treatment group and sex (P=0.01), suggesting that women may do better with standard-dose peginterferon alpha-2b.


The study was supported by Schering-Plough.

One or more authors disclosed relationships with Schering-Plough, Roche, Vertex Pharmaceuticals, GlobeImmune, Bristol-Myers Squibb, Conatus Pharmaceuticals, Pharmassett, Johnson and Johnson and Tibotec, ZymoGenetics, Biolex, Idenix, GlaxoSmithKline, Coley Pharmaceuticals, Gilead, Pfizer, Wyeth, Valeant, Romark Laboratories, Beckman, Bayer Corp., FibroScan, Kendle Phynova, LabCorp, Merck, Orasure Technologies, Ortho Diagnostics, Siemens, Debio Pharmaceuticals, Peregrine Pharmaceuticals, Intarcia, Inteercept, Genentech, Human Genome Sciences, Isis Pharmaceuticals, and Three Rivers Pharmaceuticals. Co-authors included employees of Schering-Plough.




Primary source: New England Journal of Medicine
Source reference:
McHutchison JG, et al "Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection" N Engl J Med 2009; 361: 580-93.