@article{70dea74044cf4ab5afb1809c8111b131,
title = "Factors that predict response of patients with hepatitis C virus infection to Boceprevir",
abstract = "BACKGROUND & AIMS: Little is known about factors associated with a sustained virologic response (SVR) among patients with hepatitis C virus (HCV) infection to treatment with protease inhibitors. METHODS: Previously untreated patients (from the Serine Protease Inhibitor Therapy 2 [SPRINT-2] trial) and those who did not respond to prior therapy (from the Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 [RESPOND-2] trial) received either a combination of peginterferon and ribavirin for 48 weeks or boceprevir, peginterferon, and ribavirin (triple therapy) after 4 weeks of peginterferon and ribavirin (total treatment duration, 2848 wk). A good response to interferon was defined as a <1 log10 decrease in HCV RNA at week 4; a poor response was defined as a <1 log10 decrease. We used multivariate regression analyses to identify baseline factors of the host (including the polymorphism interleukin [IL]-28B rs12979860) associated with response. The polymorphism IL-28B rs8099917 also was assessed. RESULTS: In the SPRINT-2 trial, factors that predicted a SVR to triple therapy included low viral load (odds ratio [OR], 11.6), IL-28B genotype (rs 12979860 CC vs TT and CT; ORs, 2.6 and 2.1, respectively), absence of cirrhosis (OR, 4.3), HCV subtype 1b (OR, 2.0), and non-black race (OR, 2.0). In the RESPOND-2 trial, the only factor significantly associated with a SVR was previous relapse, compared with previous nonresponse (OR, 2.6). Most patients with rs12979860 CC who received triple therapy had undetectable levels of HCV RNA by week 8 (76%89%), and were eligible for shortened therapy. In both studies, IL-28B rs12979860 CC was associated more strongly with a good response to interferon than other baseline factors; however, a <1 log10 decrease in HCV-RNA level at week 4 was associated more strongly with SVR than IL-28B rs12979860. Combining the rs8099917 and rs12979860 genotypes does not increase the association with SVR. CONCLUSIONS: The CC polymorphism at IL-28B rs12979860 is associated with response to triple therapy and can identify candidates for shorter treatment durations. A <1 log10 decrease in HCV RNA at week 4 of therapy is the strongest predictor of a SVR, regardless of polymorphisms in IL-28B. ClinicalTrials.gov; numbers NCT00705432 and NCT00708500.",
keywords = "Clinical Trial, Genetic, Prognostic Factors, Response to Therapy",
author = "Fred Poordad and Jeanpierre Bronowicki and Gordon, {Stuart C.} and Stefan Zeuzem and Jacobson, {Ira M.} and Sulkowski, {Mark S.} and Thierry Poynard and Morgan, {Timothy R.} and Cliona Molony and Pedicone, {Lisa D.} and Sings, {Heather L.} and Burroughs, {Margaret H.} and Vilma Sniukiene and Navdeep Boparai and Goteti, {Venkata S.} and Brass, {Clifford A.} and Albrecht, {Janice K.} and Bacon, {Bruce R.}",
note = "Funding Information: The authors disclose the following: Fred Poordad has received consultancy fees from Merck, Vertex, Abbott, Gilead, Achillion, Genentech, and Tibotec; has grants and grants pending from Merck ; and has received payment for the development of educational presentations and speaker fees from Merck, Genentech, Salix, and Gilead. Jean-Pierre Bronowicki has received board membership fees from Merck, Roche, Gilead, Bristol Myers Squibb, Janssen, and Bayer; consultancy fees from Merck, Boehringer Ingelheim, and Novartis; payment for lectures including service on speakers bureaus for Merck, Roche, Bayer, and Bristol Myers Squibb, and travel/accommodations/meeting expenses unrelated to activities listed from Roche. Stuart Gordon has received research support from Abbott, Anadys, Bristol Myer Squibb, Exalenz, Gilead, GlaxoSmithKline, Merck, Roche, Tibotec, and Vertex; has received lecture fees from Gilead, Merck, Vertex, and Bayer; and consulting fees from Bristol Myer Squibb, Gilead, Merck, Achillion, and CVS-Caremark. Stefan Zeuzem has received consultancy fees from Abbott, Anadys, Bristol-Myers Squibb, Gilead, HGS, Merck, Novartis, Pharmasset, Pfizer, Roche, Tibotec, and Vertex; and lecture honoraria/member of speaker's bureau for Bristol-Myers Squibb, Gilead, Merck, Novartis, and Roche. Ira Jacobson has received consultancy fees from Bristol Myers Squibb, Novartis, Gilead, Merck, Pfizer, Vertex, GlobeImmune, Boehringer-Ingelheim, Pharmasset, Tibotec, Abbott, Roche/Genentech, Achillion, and GlaxoSmithKline; has grants and grants pending from Merck , Tibotec , Abbott , Achillion , Roche/Genentech , Pharmasset , Anadys , Boehringer Ingelheim , Novartis , Gilead , Vertex , GlobeImmune , Human Genome Sciences , Pfizer , and Bristol Myers Squibb ; payment for lectures including service on speakers bureaus from Merck, Vertex, Gilead, Bristol Myers Squibb, and Roche/Genentech; and payment for the development of educational presentations from Bristol Myers Squibb, Gilead, and Vertex. Mark Sulkowski has received consultancy fees from Abbott, Bristol Myers Squibb, BIPI, Gilead, Janssen, Merck, Roche, and Vertex; and has grants and grants pending from Abbott , Bristol Myers Squibb , BIPI , Gilead , Janssen , Merck , Roche , and Vertex ; and fees for participation in review activities from Pfizer. Thierry Poynard has received board membership fees from Merck; consultancy fees from Merck and Gilead; payment for lectures including service on speakers bureaus for Merck; and has capital interest in Biopredictive. Timothy Morgan has a grant and grants pending from Bristol Myers Squibb , Merck , Roche/Genentech , Pharmasset , Gilead , and Vertex . Bruce Bacon has received consultancy fees from Gilead, Three Rivers Pharmaceuticals, Valeant, Vertex, and Human Genome Sciences; has grants and grants pending from Roche , Gilead , Bristol Myers Squibb , Three Rivers Pharmaceuticals , Valeant , Vertex , Human Genome Sciences , Wyeth , and Romark Laboratories ; payment for lectures including service on speakers bureaus for Three Rivers Pharmaceuticals, Gilead, and Merck; and served on Data and Safety Monitoring Boards for Novartis, ISIS, Vertex, and Gilead. Cliona Molony, Lisa Pedicone, Heather Sings, Margaret Burroughs, Vilma Sniukiene, Navdeep Boparai, Venkata Goteti, Clifford Brass, and Janice Albrecht, are current or former employees of Merck and may own stock or stock options in the company. ",
year = "2012",
month = sep,
doi = "10.1053/j.gastro.2012.05.011",
language = "English (US)",
volume = "143",
pages = "608--618.e5",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "3",
}