Tuesday, September 11, 2012

IL-28B polymorphism linked with boceprevir, interferon response in HCV

IL-28B polymorphism linked with boceprevir, interferon response in HCV

Poordad F. Gastroenterology. 2012;143:608-618.

A polymorphism at IL-28B rs12979860 in HCV patients was associated with response to boceprevir and interferon, with RNA decrease after 4 weeks as the strongest predictor of response, in a recent study.

The cohort consisted of patients from two previous phase 3 trials of boceprevir, including 1,048 untreated patients and 393 relapsers and partial responders. Participants received 4 weeks of pegylated interferon alfa-2b ribavirin, followed by either boceprevir or placebo for 44 weeks, or boceprevir using response-guided therapy, with treatment length adjusted to response. IL-28B genotyping was performed in 653 of the untreated patients and 259 of the relapsers and partial responders.

The CC polymorphism at the rs12979860 locus was strongly associated with interferon response compared with the CT and TT genotypes, among both previously untreated patients (OR=26.5, 7.6-92.6 for CC vs. TT; OR=16.4, 5.0-55.6 vs. CT) and those who experienced treatment failure (OR=9.3, 2.3-37.1 vs. TT; OR=3.8, 1.2-12.0 vs. CT) (95% CI for all).

Among previously untreated patients, sustained virologic response (SVR) following triple therapy was associated with the following baseline factors: Low viral load (OR=11.6, 1.5-87.8 for 400,000 IU/mL or less), IL-28B genotype (OR=2.6, 1.3-5.1 for CC compared with TT; OR=2.1, 1.2-3.7 for CC compared with CT), lack of cirrhosis (OR=4.3, 1.6-11.9), HCV genotype 1b (OR=2.0, 1.2-3.4) and non-black race (OR=2.0, 1.1-3.7) (95% CI for all). SVR was only associated with prior relapse compared with nonresponse among previous treatment failures at baseline (OR=2.6; 95% CI, 1.3-5.0).

When treatment response after 4 weeks was analyzed, IL-28B genotype was no longer predictive of response among untreated patients, while an HCV RNA decrease of 1 log10 or more was (OR=8.2, 4.5-15.0). Lower baseline RNA (OR=8.4, 1.0-68.6), no cirrhosis (OR=3.5, 1.1-11.3), BMI of 30 or less (OR=2.5, 1.4-4.2) and HCV genotype 1b (OR=2.1, 1.2-3.6) also were predictive factors. Among previous treatment failures, HCV-RNA decline (OR=2.7, 1.2-5.7) and prior relapse (OR=2.2, 1.1-4.4) were the only predictive factors (95% CI for all).

“These data suggest that knowledge of IL-28B genotype pretreatment may be used to predict which patients will have the highest likelihood of receiving a shorter duration of triple therapy, and of SVR itself,” the researchers wrote. “… IL-28B at the rs12979860 locus is the strongest pretreatment predictor of interferon responsiveness, whereas the decline in HCV-RNA level at week 4 compared with baseline is an on-treatment measurement of interferon responsiveness, and is ultimately the best overall predictor of SVR.”

Disclosure: See the study for a full list of relevant disclosures.

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