title: Predictive variables of sustained virological response after early discontinuation of triple therapy with telaprevir for genotype-1 HCV infection.
abstract: BACKGROUND
  Pivotal phase studies of telaprevir (TLV) and boceprevir (BOV) showed 10-56% rates of early treatment interruption. However, there have been no reports on the sustained virological response (SVR) rates of these patients.
  
  
  OBJECTIVE
  To assess the SVR rate in a large cohort of patients who discontinued triple therapy with TLV or BOV for reasons other than stopping rules and to identify variables predicting SVR.
  
  
  METHODS
  A survey was sent to 15 hospitals in Catalonia asking them to report all TLV/BOV treatments finished by 31 May 2014. Demographic, clinical, laboratory, liver fibrosis and therapeutic data were recorded for treatments with early discontinuation. Logistic regression analysis, ROC curves and prognostic assessment of the variables identified were calculated.
  
  
  RESULTS
  Twelve hospitals responded to the survey, representing 467 treatments and 121 (21.2%) early discontinuations, 76 (62.8%) due to stopping rules and 45 (37.2%) for other reasons. Early discontinuation was more frequent with BOV [38.2% (50/131) versus 21.1% (71/336) p<0.005], mainly due to stopping rules [78% (39/50) versus 52.1% (37/71); p=0.004]. SVR was achieved in 21/121 patients (17.4%), 19/71 (26.8%) treated with TLV and 2/50 (4.0%) treated with BOV. In patients discontinuing treatment for reasons other than stopping rules, SVR was achieved in 19/37 (55.9%) treated with TLV and in 2/11 (18.2%) treated with BOV. The SVR rate in patients treated with TLV who discontinued due to a severe adverse event was 61.5% (16/26). A logistic regression analysis was performed only with triple therapy with TLV and early discontinuation. The predictive variables of SVR were undetectable HCV-RNA at treatment week 4 and treatment length longer than 11 weeks. Treatment duration longer than 11 weeks showed the best accuracy (0.794), with a positive predictive value of 0.928.
  
  
  CONCLUSIONS
  Early discontinuation of TLV-based triple therapy due to reasons other than stopping rules still have a significant SVR rate (55.9%). Undetectable HVC-RNA at week 4 of treatment and treatment duration longer than 11 weeks are predictive of SVR in this subset of patients.
authors.affiliation: Hospital Universitario de Girona Doctor Josep Trueta, Girona, Spain. Electronic address: doroteoacero@yahoo.es.
authors.forename: Doroteo
authors.initials: D
authors.lastname: Acero Fernández
authors.affiliation: Hospital Germans Trias i Pujol, CIBERehd, Badalona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Morillas Cunill
authors.affiliation: Hospital Universitario de Girona Doctor Josep Trueta, Girona, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Ferri Iglesias
authors.affiliation: Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Torras Collell
authors.affiliation: Parc Taulí Sabadell, Hospital Universitario, Universidad Autónoma de Barcelona, CIBERehd, Sabadell, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Vergara Gómez
authors.affiliation: Hospital Arnau de Vilanova, Lleida, Spain.
authors.forename: Natividad
authors.initials: N
authors.lastname: Zaragoza Velasco
authors.affiliation: Hospital Universitario de Girona Doctor Josep Trueta, Girona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: López Nuñez
authors.affiliation: Hospital de Mútua de Terrassa, CIBERehd, Terrassa, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Forné Bardera
authors.affiliation: Hospital del Consorcio Sanitario de Mataró, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Delgado Gómez
authors.affiliation: Hospital de Viladecans, Viladecans, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Barenys Lacha
authors.affiliation: Hospital del Espíritu Santo, Santa Coloma de Gramanet, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Torres Salinas
authors.affiliation: Hospital Virgen de la Cinta, Tortosa, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Villar Fernández
authors.affiliation: Hospital de Salt, Salt, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Durández Lázaro
authors.affiliation: Hospital Clínic, CIBERehd, Barcelona, Spain.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Mariño Mendez
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019538:Health Care Surveys; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D000072230:Sustained Virologic Response; D014766:Viremia / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D012367:RNA, Viral; C486464:telaprevir; 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
keywords: Boceprevir; Chronic hepatitis C; Early discontinuation; Hepatitis crónica C; Interrupción precoz; Respuesta virológica sostenida; Sustained virological response; Telaprevir