Predictive factors for 24 weeks sustained virologic response (SVR24) and viral relapse in patients treated with simeprevir plus peginterferon and ribavirin.
BACKGROUND
Simeprevir with peginterferon and ribavirin has been used for the treatment of chronic hepatitis caused by genotype 1 hepatitis C virus (HCV). We explored the predictive factors for sustained virological response (SVR) and viral relapse using datasets from four Japanese phase 3 studies (CONCERTO).


METHODS
We used a multiple logistic regression model. First, an integrated dataset comprising 357 patients was analyzed. Subsequently, prior treatment-naïve and relapser (223 patients) and nonresponder (134 patients) of interferon-based treatment subsets were analyzed to identify predictors of SVR. A subset of nonresponders (106 patients) who were treated ≥24 weeks was also analyzed to identify predictors for viral relapse.


RESULTS
In the integrated dataset, prior treatment response was significantly associated with SVR. In subset analyses, interleukin-28B (IL28B) TT genotype and undetectable plasma HCV RNA level at week 4 were associated in treatment-naïve patients and relapsers [odds ratio (OR); 4.106 and 3.701, respectively]. In the nonresponders, the IL28B TT genotype population was very small, and inosine triphosphatase (ITPA) and undetectable plasma HCV RNA at week 4 were associated (OR; 2.506 and 3.333, respectively). Furthermore, ribavirin dose intensity (RBV-DI) and detectable plasma HCV RNA at week 4 were significantly associated with viral relapse (OR; 0.327 and 2.922, respectively).


CONCLUSIONS
IL28B and plasma HCV RNA level at week 4 were clinically relevant predictive factors for SVR in treatment-naïve patients and relapsers. Moreover, RBV-DI and plasma HCV level at week 4 were identified as relevant predictive factors for viral relapse in nonresponders.
Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan. mnakayam@its.jnj.com.
Masahiko
M
Nakayama
Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan.
Hisanori
H
Kobayashi
Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan.
Koji
K
Fukushima
Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan.
Miwako
M
Ishido
Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan.|Research and Development Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan.
Yuji
Y
Komada
Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan.
Kazutake
K
Yoshizawa
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage*; D007378:Interleukins / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000008:administration & dosage*; D000069616:Simeprevir / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult; D000095022:Interferon Lambda
D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; D012254:Ribavirin; D000069616:Simeprevir; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
Hepatitis C; Predictive factor; Ribavirin dose intensity; Simeprevir; Viral relapse