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Manns, Michael P.; McCone, Jonathan; Davis, Mitchell N.; Rossaro, Lorenzo; Schiff, Eugene; Shiffman, Mitchel L.; Bacon, Bruce; Bourliere, Marc; Sulkowski, Mark S.; Bruno, Savino; Balart, Luis; Bronowicki, Jean‐Pierre; Kwo, Paul; Poordad, Fred; Felizarta, Franco; Reddy, K. Rajender; Helmond, Frans A.; Sings, Heather L.; Pedicone, Lisa D.; Burroughs, Margaret; Brass, Clifford A.; Albrecht, Janice K.; Vierling, John M.

Overall safety profile of boceprevir plus peginterferon alfa‐2b and ribavirin in patients with chronic hepatitis C genotype 1: a combined analysis of 3 phase 2/3 clinical trials

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  • Media type: E-Article
  • Title: Overall safety profile of boceprevir plus peginterferon alfa‐2b and ribavirin in patients with chronic hepatitis C genotype 1: a combined analysis of 3 phase 2/3 clinical trials
  • Contributor: Manns, Michael P.; McCone, Jonathan; Davis, Mitchell N.; Rossaro, Lorenzo; Schiff, Eugene; Shiffman, Mitchel L.; Bacon, Bruce; Bourliere, Marc; Sulkowski, Mark S.; Bruno, Savino; Balart, Luis; Bronowicki, Jean‐Pierre; Kwo, Paul; Poordad, Fred; Felizarta, Franco; Reddy, K. Rajender; Helmond, Frans A.; Sings, Heather L.; Pedicone, Lisa D.; Burroughs, Margaret; Brass, Clifford A.; Albrecht, Janice K.; Vierling, John M.
  • imprint: Wiley, 2014
  • Published in: Liver International
  • Language: English
  • DOI: 10.1111/liv.12300
  • ISSN: 1478-3223; 1478-3231
  • Keywords: Hepatology
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background &amp; Aims</jats:title><jats:p>Triple therapy with peginterferon/ribavirin (<jats:styled-content style="fixed-case">PR</jats:styled-content>) plus an <jats:styled-content style="fixed-case">NS</jats:styled-content>3 protease inhibitor has emerged as the standard‐of‐care for patients with chronic hepatitis C genotype‐1. We provide a detailed safety analysis comparing <jats:styled-content style="fixed-case">PR</jats:styled-content> to boceprevir plus <jats:styled-content style="fixed-case">PR</jats:styled-content> (<jats:styled-content style="fixed-case">BOC</jats:styled-content>/<jats:styled-content style="fixed-case">PR</jats:styled-content>) across three phase 2/3 studies.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p><jats:styled-content style="fixed-case">SPRINT</jats:styled-content>‐1 was an open‐label phase 2 study in 595 treatment‐naive patients. In the two phase 3 studies, 1500 patients (1097 treatment‐naive, <jats:styled-content style="fixed-case">SPRINT</jats:styled-content>‐2; 403 treatment‐failure, <jats:styled-content style="fixed-case">RESPOND</jats:styled-content>‐2) were randomized to receive <jats:styled-content style="fixed-case">PR</jats:styled-content> alone, or one of two regimens where <jats:styled-content style="fixed-case">BOC</jats:styled-content> was added to <jats:styled-content style="fixed-case">PR</jats:styled-content> after a 4‐wk <jats:styled-content style="fixed-case">PR</jats:styled-content> lead‐in. In this analysis, the respective <jats:styled-content style="fixed-case">BOC</jats:styled-content>/<jats:styled-content style="fixed-case">PR</jats:styled-content> and <jats:styled-content style="fixed-case">PR</jats:styled-content> arms were combined for all three trials. The benefit of shortened duration of treatment using response‐guided therapy (<jats:styled-content style="fixed-case">RGT</jats:styled-content>) was also explored in the <jats:styled-content style="fixed-case">SPRINT</jats:styled-content>‐2 trial.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Only two adverse events, anaemia and dysgeusia, occurred 20% more often with the <jats:styled-content style="fixed-case">BOC</jats:styled-content>‐containing regimens compared with <jats:styled-content style="fixed-case">PR</jats:styled-content>. Nausea, diarrhoea and neutropenia were the only other common events with an incidence of at least 5% greater when <jats:styled-content style="fixed-case">BOC</jats:styled-content> was added to the <jats:styled-content style="fixed-case">PR</jats:styled-content> backbone. The proportions of patients reporting serious adverse events (AE), life‐threatening <jats:styled-content style="fixed-case">AE</jats:styled-content>s, and study drug discontinuation because of an <jats:styled-content style="fixed-case">AE</jats:styled-content> were similar in the <jats:styled-content style="fixed-case">PR</jats:styled-content> and <jats:styled-content style="fixed-case">BOC</jats:styled-content>/<jats:styled-content style="fixed-case">PR</jats:styled-content> arms. In treatment‐naive patients, <jats:styled-content style="fixed-case">RGT</jats:styled-content> generally did not result in a lower frequency of common <jats:styled-content style="fixed-case">AE</jats:styled-content>s; however, <jats:styled-content style="fixed-case">RGT</jats:styled-content> led to decreased exposure to all 3 study drugs and to a decrease in the mean duration of several clinically relevant <jats:styled-content style="fixed-case">AE</jats:styled-content>s such as anaemia, neutropenia, fatigue and depression, as well as earlier normalization of haemoglobin and neutrophil counts.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The safety profile of <jats:styled-content style="fixed-case">BOC</jats:styled-content> combination therapy largely reflects the known profile of peginterferon and ribavirin, with incremental haematolgical effects and dysgeusia. Shorter treatment duration with <jats:styled-content style="fixed-case">RGT</jats:styled-content> significantly reduced the duration of <jats:styled-content style="fixed-case">AE</jats:styled-content>s.</jats:p></jats:sec>