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Favorable adverse event profile of sofosbuvir/ribavirin compared to boceprevir/interferon/ribavirin for treatment of hepatitis C

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Abstract

Background

Triple therapy for the treatment of hepatitis C virus (HCV) with first-generation directly acting antiviral agents, the non-structural serine protease inhibitors boceprevir (BOC) and telaprevir have resulted in improved sustained virologic response (SVR) rates. However, a high incidence of adverse events (AEs), high pill burdens and drug interactions remain significant barriers to successful completion of therapy. The aim of this study was to evaluate the AEs observed with BOC triple therapy in comparison to IFN-free sofosbuvir/ribavirin (SOF/RBV) therapy in HCV monoinfected, genotype-1 (GT-1) individuals.

Methods

We retrospectively evaluated HCV monoinfected, treatment-naïve or -experienced, GT-1 individuals treated with either BOC/IFN/RBV at the Veterans Affairs Medical Center, Baltimore (n = 97) or SOF/RBV in the NIAID SPARE clinical trial (n = 60). AEs, namely hematologic (hemoglobin, neutrophil and platelet counts), hepatic (alanine transaminase or bilirubin) and renal (eGFR), were measured according to the DAIDS toxicity table (version 1.0).

Results

BOC/IFN/RBV was associated with significantly more AEs, most commonly neutropenia, anemia and thrombocytopenia. In the SOF/RBV cohort, five (8 %) patients discontinued treatment early, but none (0 %) were because of AEs, while 60 (62 %) patients on triple therapy discontinued treatment early, 34 (57 %) because of AEs. SVR24 rates were 68 versus 34 % with SOF/RBV versus BOC/IFN/RBV.

Conclusions

SOF/RBV treatment was associated with fewer side effects than BOC-based triple therapy, appearing to be a safer and more tolerable alternative for HCV GT-1 subjects. These results show that emerging IFN-free therapies may enhance patient adherence, allowing treatment of larger number of patients with improved efficacy.

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Acknowledgements

We would like to acknowledge the contributions of the following individuals: Laura Heytens, who was the study coordinator on the SPARE study. This research was supported in part by the intramural program of the National Institute of Allergy and Infectious Diseases. The data from this study have been partially presented at The Conference for Retroviruses and Opportunistic Infections (CROI) 2014 in Boston, MA, USA.

Compliance with ethical requirements and Conflict of interest

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study. Rohit Talwani has served as a speaker for Merck and performs research funded by Vertex Pharmaceuticals. Shivakumar Narayanan, Kerry Townsend, Thomas Macharia, Adrian Majid, Amy Nelson, Robert Redfield, Shyam Kottilil, Rohit Talwani and Anu Osinusi have no conflicts of interest to report.

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Authors and Affiliations

  1. Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA

    Shivakumar Narayanan, Thomas Macharia, Adrian Majid, Robert R. Redfield, Rohit Talwani & Anu Osinusi

  2. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10/11N204, 9000 Rockville Pike, Bethesda, MD, 20892, USA

    Kerry Townsend, Amy Nelson, Shyam Kottilil & Anu Osinusi

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  1. Shivakumar Narayanan
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  2. Kerry Townsend
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  3. Thomas Macharia
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  4. Adrian Majid
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  5. Amy Nelson
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  6. Robert R. Redfield
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  7. Shyam Kottilil
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  8. Rohit Talwani
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  9. Anu Osinusi
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Correspondence to Shyam Kottilil.

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Disclaimer: The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government.

Shivakumar Narayanan and Kerry Townsend contributed equally to this work.

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Narayanan, S., Townsend, K., Macharia, T. et al. Favorable adverse event profile of sofosbuvir/ribavirin compared to boceprevir/interferon/ribavirin for treatment of hepatitis C. Hepatol Int 8, 560–566 (2014). https://doi.org/10.1007/s12072-014-9574-0

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  • DOI: https://doi.org/10.1007/s12072-014-9574-0

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