title: Prediction of treatment week eight response & sustained virologic response in patients treated with boceprevir plus peginterferon alfa and ribavirin.
abstract: OBJECTIVE
  Sustained virologic response (SVR) can be attained with boceprevir plus peginterferon alfa and ribavirin (PR) in up to 68% of patients, and short duration therapy is possible if plasma HCV RNA levels are undetectable at treatment week 8 (TW8 response). We have developed predictive models for SVR, and TW8 response using data from boceprevir clinical trials.
  
  
  METHODS
  Regression models were built to predict TW8 response and SVR. Separate models were built for TW8 and SVR using baseline variables only, and compared to models with baseline variables plus HCV RNA change after 4 weeks of PR (TW4 delta). Predictive accuracy was assessed by c-statistics, calibration curves, and decision curve analyses. Nomograms were developed to create clinical decision support tools. Models were externally validated using independent data.
  
  
  RESULTS
  The models that included TW4 delta produced the best discrimination ability. The predictive factors for TW8 response (n = 856) were TW4 delta, race, platelet count and ALT. The predictive factors for SVR (n = 522) were TW4 delta, HCV-subtype, gender, BMI, RBV dose and platelet count. The discrimination abilities of these models were excellent (C-statistics = 0.88, 0.80 respectively). Baseline models for TW8 response (n = 444) and SVR (n = 197) had weaker discrimination ability (C-statistic = 0.76, 0.69). External validation confirmed the predictive accuracy of the week 4 models.
  
  
  CONCLUSIONS
  Models incorporating baseline and treatment week 4 data provide excellent prediction of TW8 response and SVR, and support the clinical utility of the lead-in phase of PR. The nomograms are suitable for point-of-care use to inform individual patient and physician decision-making.
authors.affiliation: Department of Gastroenterology, St. Vincent's Hospital, Melbourne, VIC, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Thompson
authors.affiliation: Merck, Whitehouse Station, New Jersey, United States of America.
authors.forename: Scott
authors.initials: S
authors.lastname: Devine
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Mike
authors.initials: M
authors.lastname: Kattan
authors.affiliation: Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Muir
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003663:Decision Trees; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015203:Reproducibility of Results; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline
references.citation: Hepatology. 2012 Aug;56(2):567-75
references.pmid: 22619063
references.citation: N Engl J Med. 2011 Jun 23;364(25):2405-16
references.pmid: 21696307
references.citation: Med Decis Making. 2006 Nov-Dec;26(6):565-74
references.pmid: 17099194
references.citation: N Engl J Med. 2011 Jun 23;364(25):2417-28
references.pmid: 21696308
references.citation: Hepatology. 2003 Mar;37(3):600-9
references.pmid: 12601358
references.citation: N Engl J Med. 2011 Mar 31;364(13):1195-206
references.pmid: 21449783
references.citation: Intervirology. 2009;52(5):247-51
references.pmid: 19602898
references.citation: Stat Med. 1984 Apr-Jun;3(2):143-52
references.pmid: 6463451
references.citation: Liver Int. 2009 Jan;29 Suppl 1:74-81
references.pmid: 19207969
references.citation: Clin Gastroenterol Hepatol. 2013 Jan;11(1):81-87.e4; quiz e5
references.pmid: 23064222
references.citation: Gastroenterology. 2012 Sep;143(3):608-618.e5
references.pmid: 22626609
references.citation: N Engl J Med. 2011 Mar 31;364(13):1207-17
references.pmid: 21449784
references.citation: Lancet. 2010 Aug 28;376(9742):705-16
references.pmid: 20692693