1. Factors that predict response of patients with hepatitis C virus infection to boceprevir
- Author
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Poordad, Fred, Bronowicki, Jeanpierre, Gordon, Stuart C., Zeuzem, Stefan, Jacobson, Ira M., Sulkowski, Mark S., Poynard, Thierry, Morgan, Timothy R., Molony, Cliona, Pedicone, Lisa D., Sings, Heather L., Burroughs, Margaret H., Sniukiene, Vilma, Boparai, Navdeep, Goteti, Venkata S., Brass, Clifford A., Albrecht, Janice K., Bacon, Bruce R., Sprint, 2, Respond, 2 Investigators, Taliani, Gloria, Cedars-Sinai Medical Center, Centre Hospitalier Universitaire de Nancy (CHU Nancy), Université Henri Poincaré - Nancy 1 (UHP), Henry Ford Hospital, Goethe-University Frankfurt am Main, Weill Medical College of Cornell University [New York], California State University [Long Beach] (CSULB ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Merck & Co. Inc, Saint Louis University (SLU), Hepatology and Liver Transplantation, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Johann Wolfgang Goethe University Medical Center, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Poordad, F, Bronowicki, JP, Gordon, SC, Zeuzem, S, Jacobson, IM, Sulkowski, MS, Poynard, T, Morgan, TR, Molony, C, Pedicone, LD, Sings, HL, Burroughs, MH, Sniukiene, V, Boparai, N, Goteti, VS, Brass, CA, Albrecht, JK, Bacon, BR, Craxi, A, and SPRINT-2 and RESPOND-2 Investigators
- Subjects
Male ,Cirrhosis ,MESH: Logistic Models ,Hepacivirus ,MESH: Risk Assessment ,Gastroenterology ,Polyethylene Glycols ,MESH: Recombinant Proteins ,MESH: Genotype ,0302 clinical medicine ,Odds Ratio ,Prospective Studies ,MESH: Treatment Outcome ,Response to Therapy ,0303 health sciences ,MESH: Polymorphism, Single Nucleotide ,virus diseases ,3. Good health ,MESH: RNA, Viral ,HCV ,Drug Therapy, Combination ,030211 gastroenterology & hepatology ,Clinical Trial ,Genetic ,Prognostic Factors ,Adult ,Antiviral Agents ,Biomarkers ,Canada ,Europe ,Female ,Genotype ,Hepatitis C ,Humans ,Interferon-alpha ,Interleukins ,Logistic Models ,Multivariate Analysis ,Phenotype ,Polymorphism, Single Nucleotide ,Proline ,RNA, Viral ,Recombinant Proteins ,Ribavirin ,Risk Assessment ,Risk Factors ,Time Factors ,Treatment Outcome ,United States ,Viral Load ,Viral load ,medicine.medical_specialty ,MESH: Interleukins ,Interferon alpha-2 ,MESH: Phenotype ,03 medical and health sciences ,Drug Therapy ,MESH: Ribavirin ,MESH: Canada ,Boceprevir ,Polymorphism ,MESH: Proline ,MESH: Humans ,MESH: Adult ,Odds ratio ,medicine.disease ,digestive system diseases ,Clinical trial ,chemistry ,Immunology ,MESH: Female ,medicine.disease_cause ,chemistry.chemical_compound ,Interferon ,MESH: Risk Factors ,MESH: Hepacivirus ,Viral ,Single Nucleotide ,Combination ,MESH: Interferon-alpha ,MESH: Viral Load ,medicine.drug ,MESH: Antiviral Agents ,Hepatitis C virus ,MESH: Multivariate Analysis ,Internal medicine ,medicine ,MESH: United States ,030304 developmental biology ,MESH: Hepatitis C ,Hepatology ,business.industry ,MESH: Time Factors ,MESH: Biological Markers ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,MESH: Prospective Studies ,MESH: Male ,MESH: Odds Ratio ,MESH: Drug Therapy, Combination ,MESH: Polyethylene Glycols ,RNA ,Interferons ,MESH: Europe ,business - 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, 28–48 wk). A good response to interferon was defined as a ≥1 log 10 decrease in HCV RNA at week 4; a poor response was defined as a 10 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 log 10 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 log 10 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.
- Published
- 2012