Premium
Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial
Author(s) -
Younossi Zobair,
Negro Francesco,
Serfaty Lawrence,
Pol Stanislas,
Diago Moises,
Zeuzem Stefan,
Andreone Pietro,
Lawitz Eric J.,
Roberts Stuart,
Focaccia Roberto,
Foster Graham R.,
Horban Andrzej,
LonjonDomanec Isabelle,
Coate Bruce,
DeMasi Ralph,
Picchio Gaston,
Witek James
Publication year - 2013
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.26437
Subject(s) - telaprevir , medicine , ribavirin , gastroenterology , interquartile range , insulin resistance , homeostatic model assessment , univariate analysis , confidence interval , hepatitis c , pegylated interferon , body mass index , insulin , hepatitis c virus , immunology , multivariate analysis , virus
Baseline homeostasis model assessment‐estimated insulin resistance (HOMA‐IR), a marker for insulin resistance, has been associated with poor virologic response to peginterferon alpha/ribavirin (PR) in chronic hepatitis C. We evaluated the association between baseline HOMA‐IR and pretreatment factors on sustained virologic response (SVR) to telaprevir (TVR) in genotype 1 patients with hepatitis C and prior peginterferon/ribavirin (PR) treatment failure. Patients were randomized to 12 weeks of TVR (750 mg q8h) plus peginterferon (180 μg/week) and ribavirin (1,000‐1,200 mg/day) (with or without a 4‐week lead‐in) followed by PR, or PR alone (PR48), for 48 weeks. Univariate and multiple logistic regression analyses explored the prognostic significance of baseline HOMA‐IR alone and adjusted for other pretreatment factors and SVR. The TVR arms were pooled for the purposes of this analysis. In all, 662 patients were randomized; 578 had baseline HOMA‐IR and other prognostic data and were included in this analysis. Median baseline HOMA‐IR was 2.6 (interquartile range [IQR] 1.7‐4.3); 207 (36%), 206 (36%), and 165 (29%) patients had baseline HOMA‐IR <2, 2 to <4, and ≥4, respectively. Male gender, higher body mass index, triglycerides, gamma‐glutamyl transpeptidase, maximum alanine aminotransferase/aspartate aminotransferase, and fibrosis stage were associated with higher baseline HOMA‐IR. Baseline HOMA‐IR was associated with SVR in univariate analysis, but not after adjustment for other baseline prognostic factors (TVR: OR = 0.95, 95% confidence interval [CI]: 0.71,1.29; PR48: 0.60; 95% CI: 0.25,1.43). Conclusion : In patients with prior PR treatment failure, baseline HOMA‐IR correlated with SVR in univariate but not multivariate analyses, suggesting other factors have a more direct causal relationship with virologic response to TVR‐based therapy than HOMA‐IR. (H epatology 2013; 58:1897–1906)