Analysis Provides Insight on Negative Predictors of SVR12
WASHINGTON — Patients with hepatitis C virus who received the 3D regimen and had fewer than four predictors of negative response experienced 12-week sustained virologic response rates above 95%, according to findings presented here.
“The presence of cirrhosis, null response to pegylated interferon and ribavirin, IL28B non-cc genotype and high baseline viral load were not significant negative predictors of response,” Nancy Reau, MD, of the University of Chicago Medical Center, said during her presentation. “It’s easy to see that most of the characteristics we normally assign value are not incredibly impactful.”
Reau and colleagues, reviewed six phase 3 studies involving patients with genotype 1 HCV treated with Viekira Pak (ombitasvir, paritaprevir, ritonavir plus dasabuvir; AbbVie) with or without ribavirin.
She suggested that these patients have achieved encouraging SVR12 rates regardless of host, viral and disease characteristics. The researchers aimed to investigate whether multiple negative predictors of response meaningfully impacted outcomes.
The analysis included more than 2,000 patients from the SAPPHIRE-I, SAPPHIRE-II, TURQUOISE-II, PEARL-II, PEARL-III and PEARL-IV studies.
“Twenty-two continuous and categorical baseline variables were included in the analysis performed on two populations,” Reau said. “All patients with data available were included regardless of whether they received a label-recommended regimen.”
The factors that underwent analysis included age, baseline BMI, weight, HCV RNA and alanine aminotransferase level. Other independent categorical variables included HCV sub-genotype, IL28B genotype, sex, race, ethnicity, geographic region, fibrosis stage, cirrhosis, treatment regimen (with or without ribavirin), treatment duration (12 or 24 weeks for patients with cirrhosis), treatment experience and history of diabetes, depression or bipolar disorder, bleeding disorders and former injection drug use.
When considering all genotypes, genotype 1a disease was independently associated with reduced SVR12, with a rate of 94%. Other factors associated with lower SVR12 included higher weight at baseline, IL28B TT genotype, Hispanic/Latino ethnicity and higher baseline HCV RNA, according to Reau.
The SVR12 rate for the entire cohort was 96.2%. Among patients with zero or one predictor of poor outcome, the SVR12 rate was 99%. Two predictors yielded an SVR12 rate of 97%, and three predictors yielded 95% SVR12.
However, SVR12 rates were 86% for patients with four negative predictors and 82% for five predictors.
When considering just those 1083 patients that received label recommended 3D based on cirrhosis status and HCV subgenotype, “Of the 22 variables, only two had a negative impact in the multivariate stepwise analysis,” Reau said. “Those included BMI and HCV genotype 1a disease.”
The SVR12 rate in that group was 97%; even those that had both factors had SVR rates of 95% or greater, Reau explained.
For more information:
Reau NS, et al. Abstract 1013. Presented at: Digestive Disease Week, May 16-19, 2015; Washington, D.C.
Disclosure: Reau reports associations with a number of device and pharmaceutical companies. Please see the DDW faculty disclosure index for all other researchers’ relevant financial disclosures.