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

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

doi:10.1111/liv.12300

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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Background & Aims: Triple therapy with peginterferon/ribavirin (PR) plus an NS3 protease inhibitor has emerged as the standard-of-care for patients with chronic hepatitis C genotype-1. We provide a detailed safety analysis comparing PR to boceprevir plus PR (BOC/PR) across three phase 2/3 studies. Methods: SPRINT-1 was an open-label phase 2 study in 595 treatment-naive patients. In the two phase 3 studies, 1500 patients (1097 treatment-naive, SPRINT-2; 403 treatment-failure, RESPOND-2) were randomized to receive PR alone, or one of two regimens where BOC was added to PR after a 4-wk PR lead-in. In this analysis, the respective BOC/PR and PR arms were combined for all three trials. The benefit of shortened duration of treatment using response-guided therapy (RGT) was also explored in the SPRINT-2 trial. Results: Only two adverse events, anaemia and dysgeusia, occurred 20% more often with the BOC-containing regimens compared with PR. Nausea, diarrhoea and neutropenia were the only other common events with an incidence of at least 5% greater when BOC was added to the PR backbone. The proportions of patients reporting serious adverse events (AE), life-threatening AEs, and study drug discontinuation because of an AE were similar in the PR and BOC/PR arms. In treatment-naive patients, RGT generally did not result in a lower frequency of common AEs; however, RGT led to decreased exposure to all 3 study drugs and to a decrease in the mean duration of several clinically relevant AEs such as anaemia, neutropenia, fatigue and depression, as well as earlier normalization of haemoglobin and neutrophil counts. Conclusions: The safety profile of BOC combination therapy largely reflects the known profile of peginterferon and ribavirin, with incremental haematolgical effects and dysgeusia. Shorter treatment duration with RGT significantly reduced the duration of AEs.

Original language	English (US)
Pages (from-to)	707-719
Number of pages	13
Journal	Liver International
Volume	34
Issue number	5
DOIs	https://doi.org/10.1111/liv.12300
State	Published - May 2014

Keywords

Antiviral therapy
Victrelis

ASJC Scopus subject areas

Hepatology

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10.1111/liv.12300

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Manns, M. P., Mccone, J., Davis, M. N., Rossaro, L., Schiff, E., Shiffman, M. L., Bacon, B., Bourliere, M., Sulkowski, M. S., Bruno, S., Balart, L., Bronowicki, J. P., Kwo, P., Poordad, F., Felizarta, F., Reddy, K. R., Helmond, F. A., Sings, H. L., Pedicone, L. D., ... Vierling, J. M. (2014). 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. Liver International, 34(5), 707-719. https://doi.org/10.1111/liv.12300

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. / Manns, Michael P.; Mccone, Jonathan; Davis, Mitchell N. et al.
In: Liver International, Vol. 34, No. 5, 05.2014, p. 707-719.

Research output: Contribution to journal › Article › peer-review

Manns, MP, Mccone, J, Davis, MN, Rossaro, L, Schiff, E, Shiffman, ML, Bacon, B, Bourliere, M, Sulkowski, MS, Bruno, S, Balart, L, Bronowicki, JP, Kwo, P, Poordad, F, Felizarta, F, Reddy, KR, Helmond, FA, Sings, HL, Pedicone, LD, Burroughs, M, Brass, CA, Albrecht, JK & Vierling, JM 2014, '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', Liver International, vol. 34, no. 5, pp. 707-719. https://doi.org/10.1111/liv.12300

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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",

abstract = "Background & Aims: Triple therapy with peginterferon/ribavirin (PR) plus an NS3 protease inhibitor has emerged as the standard-of-care for patients with chronic hepatitis C genotype-1. We provide a detailed safety analysis comparing PR to boceprevir plus PR (BOC/PR) across three phase 2/3 studies. Methods: SPRINT-1 was an open-label phase 2 study in 595 treatment-naive patients. In the two phase 3 studies, 1500 patients (1097 treatment-naive, SPRINT-2; 403 treatment-failure, RESPOND-2) were randomized to receive PR alone, or one of two regimens where BOC was added to PR after a 4-wk PR lead-in. In this analysis, the respective BOC/PR and PR arms were combined for all three trials. The benefit of shortened duration of treatment using response-guided therapy (RGT) was also explored in the SPRINT-2 trial. Results: Only two adverse events, anaemia and dysgeusia, occurred 20% more often with the BOC-containing regimens compared with PR. Nausea, diarrhoea and neutropenia were the only other common events with an incidence of at least 5% greater when BOC was added to the PR backbone. The proportions of patients reporting serious adverse events (AE), life-threatening AEs, and study drug discontinuation because of an AE were similar in the PR and BOC/PR arms. In treatment-naive patients, RGT generally did not result in a lower frequency of common AEs; however, RGT led to decreased exposure to all 3 study drugs and to a decrease in the mean duration of several clinically relevant AEs such as anaemia, neutropenia, fatigue and depression, as well as earlier normalization of haemoglobin and neutrophil counts. Conclusions: The safety profile of BOC combination therapy largely reflects the known profile of peginterferon and ribavirin, with incremental haematolgical effects and dysgeusia. Shorter treatment duration with RGT significantly reduced the duration of AEs.",

keywords = "Antiviral therapy, Victrelis",

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

year = "2014",

month = may,

doi = "10.1111/liv.12300",

language = "English (US)",

volume = "34",

pages = "707--719",

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T1 - Overall safety profile of boceprevir plus peginterferon alfa-2b and ribavirin in patients with chronic hepatitis C genotype 1

T2 - A combined analysis of 3 phase 2/3 clinical trials

AU - Manns, Michael P.

AU - Mccone, Jonathan

AU - Davis, Mitchell N.

AU - Rossaro, Lorenzo

AU - Schiff, Eugene

AU - Shiffman, Mitchel L.

AU - Bacon, Bruce

AU - Bourliere, Marc

AU - Sulkowski, Mark S.

AU - Bruno, Savino

AU - Balart, Luis

AU - Bronowicki, Jean Pierre

AU - Kwo, Paul

AU - Poordad, Fred

AU - Felizarta, Franco

AU - Reddy, K. Rajender

AU - Helmond, Frans A.

AU - Sings, Heather L.

AU - Pedicone, Lisa D.

AU - Burroughs, Margaret

AU - Brass, Clifford A.

AU - Albrecht, Janice K.

AU - Vierling, John M.

PY - 2014/5

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N2 - Background & Aims: Triple therapy with peginterferon/ribavirin (PR) plus an NS3 protease inhibitor has emerged as the standard-of-care for patients with chronic hepatitis C genotype-1. We provide a detailed safety analysis comparing PR to boceprevir plus PR (BOC/PR) across three phase 2/3 studies. Methods: SPRINT-1 was an open-label phase 2 study in 595 treatment-naive patients. In the two phase 3 studies, 1500 patients (1097 treatment-naive, SPRINT-2; 403 treatment-failure, RESPOND-2) were randomized to receive PR alone, or one of two regimens where BOC was added to PR after a 4-wk PR lead-in. In this analysis, the respective BOC/PR and PR arms were combined for all three trials. The benefit of shortened duration of treatment using response-guided therapy (RGT) was also explored in the SPRINT-2 trial. Results: Only two adverse events, anaemia and dysgeusia, occurred 20% more often with the BOC-containing regimens compared with PR. Nausea, diarrhoea and neutropenia were the only other common events with an incidence of at least 5% greater when BOC was added to the PR backbone. The proportions of patients reporting serious adverse events (AE), life-threatening AEs, and study drug discontinuation because of an AE were similar in the PR and BOC/PR arms. In treatment-naive patients, RGT generally did not result in a lower frequency of common AEs; however, RGT led to decreased exposure to all 3 study drugs and to a decrease in the mean duration of several clinically relevant AEs such as anaemia, neutropenia, fatigue and depression, as well as earlier normalization of haemoglobin and neutrophil counts. Conclusions: The safety profile of BOC combination therapy largely reflects the known profile of peginterferon and ribavirin, with incremental haematolgical effects and dysgeusia. Shorter treatment duration with RGT significantly reduced the duration of AEs.

AB - Background & Aims: Triple therapy with peginterferon/ribavirin (PR) plus an NS3 protease inhibitor has emerged as the standard-of-care for patients with chronic hepatitis C genotype-1. We provide a detailed safety analysis comparing PR to boceprevir plus PR (BOC/PR) across three phase 2/3 studies. Methods: SPRINT-1 was an open-label phase 2 study in 595 treatment-naive patients. In the two phase 3 studies, 1500 patients (1097 treatment-naive, SPRINT-2; 403 treatment-failure, RESPOND-2) were randomized to receive PR alone, or one of two regimens where BOC was added to PR after a 4-wk PR lead-in. In this analysis, the respective BOC/PR and PR arms were combined for all three trials. The benefit of shortened duration of treatment using response-guided therapy (RGT) was also explored in the SPRINT-2 trial. Results: Only two adverse events, anaemia and dysgeusia, occurred 20% more often with the BOC-containing regimens compared with PR. Nausea, diarrhoea and neutropenia were the only other common events with an incidence of at least 5% greater when BOC was added to the PR backbone. The proportions of patients reporting serious adverse events (AE), life-threatening AEs, and study drug discontinuation because of an AE were similar in the PR and BOC/PR arms. In treatment-naive patients, RGT generally did not result in a lower frequency of common AEs; however, RGT led to decreased exposure to all 3 study drugs and to a decrease in the mean duration of several clinically relevant AEs such as anaemia, neutropenia, fatigue and depression, as well as earlier normalization of haemoglobin and neutrophil counts. Conclusions: The safety profile of BOC combination therapy largely reflects the known profile of peginterferon and ribavirin, with incremental haematolgical effects and dysgeusia. Shorter treatment duration with RGT significantly reduced the duration of AEs.

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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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