Effects of ribavirin dose reduction vs erythropoietin for boceprevir-related anemia in patients with chronic hepatitis C virus genotype 1 infection - A randomized trial

Fred Poordad, Eric Lawitz, K. Rajender Reddy, Nezam H. Afdhal, Christophe Hézode, Stefan Zeuzem, Samuel S. Lee, Jose Luis Calleja, Robert S. Brown, Antonio Craxi, Heiner Wedemeyer, Lisa Nyberg, David R. Nelson, Lorenzo Rossaro, Luis Balart, Timothy R. Morgan, Bruce R. Bacon, Steven L. Flamm, Kris V. Kowdley, Weiping DengKenneth J. Koury, Lisa D. Pedicone, Frank J. Dutko, Margaret H. Burroughs, Katia Alves, Janice Wahl, Clifford A. Brass, Janice K. Albrecht, Mark S. Sulkowski

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Background & Aims Treatment of hepatitis C virus (HCV) infection with boceprevir, peginterferon, and ribavirin can lead to anemia, which has been managed by reducing ribavirin dose and/or erythropoietin therapy. We assessed the effects of these anemia management strategies on rates of sustained virologic response (SVR) and safety. Methods Patients (n = 687) received 4 weeks of peginterferon and ribavirin followed by 24 or 44 weeks of boceprevir (800 mg, 3 times each day) plus peginterferon and ribavirin. Patients who became anemic (levels of hemoglobin approximately ≤10 g/dL) during the study treatment period (n = 500) were assigned to groups that were managed by ribavirin dosage reduction (n = 249) or erythropoietin therapy (n = 251). Results Rates of SVR were comparable between patients whose anemia was managed by ribavirin dosage reduction (71.5%) vs erythropoietin therapy (70.9%), regardless of the timing of the first intervention to manage anemia or the magnitude of ribavirin dosage reduction. There was a threshold for the effect on rate of SVR: patients who received <50% of the total milligrams of ribavirin assigned by the protocol had a significantly lower rate of SVR (P <.0001) than those who received ≥50%. Among patients who did not develop anemia, the rate of SVR was 40.1%. Eleven thromboembolic adverse events were reported in 9 of 295 patients who received erythropoietin, compared with 1 of 392 patients who did not receive erythropoietin. Conclusions Reduction of ribavirin dosage can be the primary approach for management of anemia in patients receiving peginterferon, ribavirin, and boceprevir for HCV infection. Reduction in ribavirin dosage throughout the course of triple therapy does not affect rates of SVR. However, it is important that the patient receives at least 50% of the total amount (milligrams) of ribavirin assigned by response-guided therapy. ClinicalTrials.gov number, NCT01023035.

Original languageEnglish (US)
JournalGastroenterology
Volume145
Issue number5
DOIs
StatePublished - Nov 2013

Fingerprint

Ribavirin
Chronic Hepatitis C
Erythropoietin
Hepacivirus
Anemia
Genotype
Infection
Virus Diseases
Therapeutics
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
Sustained Virologic Response
Hemoglobins

Keywords

  • DAA
  • EPO
  • Erythropoiesis
  • Side Effect

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Effects of ribavirin dose reduction vs erythropoietin for boceprevir-related anemia in patients with chronic hepatitis C virus genotype 1 infection - A randomized trial. / Poordad, Fred; Lawitz, Eric; Reddy, K. Rajender; Afdhal, Nezam H.; Hézode, Christophe; Zeuzem, Stefan; Lee, Samuel S.; Calleja, Jose Luis; Brown, Robert S.; Craxi, Antonio; Wedemeyer, Heiner; Nyberg, Lisa; Nelson, David R.; Rossaro, Lorenzo; Balart, Luis; Morgan, Timothy R.; Bacon, Bruce R.; Flamm, Steven L.; Kowdley, Kris V.; Deng, Weiping; Koury, Kenneth J.; Pedicone, Lisa D.; Dutko, Frank J.; Burroughs, Margaret H.; Alves, Katia; Wahl, Janice; Brass, Clifford A.; Albrecht, Janice K.; Sulkowski, Mark S.

In: Gastroenterology, Vol. 145, No. 5, 11.2013.

Research output: Contribution to journalArticle

Poordad, F, Lawitz, E, Reddy, KR, Afdhal, NH, Hézode, C, Zeuzem, S, Lee, SS, Calleja, JL, Brown, RS, Craxi, A, Wedemeyer, H, Nyberg, L, Nelson, DR, Rossaro, L, Balart, L, Morgan, TR, Bacon, BR, Flamm, SL, Kowdley, KV, Deng, W, Koury, KJ, Pedicone, LD, Dutko, FJ, Burroughs, MH, Alves, K, Wahl, J, Brass, CA, Albrecht, JK & Sulkowski, MS 2013, 'Effects of ribavirin dose reduction vs erythropoietin for boceprevir-related anemia in patients with chronic hepatitis C virus genotype 1 infection - A randomized trial', Gastroenterology, vol. 145, no. 5. https://doi.org/10.1053/j.gastro.2013.07.051
Poordad, Fred ; Lawitz, Eric ; Reddy, K. Rajender ; Afdhal, Nezam H. ; Hézode, Christophe ; Zeuzem, Stefan ; Lee, Samuel S. ; Calleja, Jose Luis ; Brown, Robert S. ; Craxi, Antonio ; Wedemeyer, Heiner ; Nyberg, Lisa ; Nelson, David R. ; Rossaro, Lorenzo ; Balart, Luis ; Morgan, Timothy R. ; Bacon, Bruce R. ; Flamm, Steven L. ; Kowdley, Kris V. ; Deng, Weiping ; Koury, Kenneth J. ; Pedicone, Lisa D. ; Dutko, Frank J. ; Burroughs, Margaret H. ; Alves, Katia ; Wahl, Janice ; Brass, Clifford A. ; Albrecht, Janice K. ; Sulkowski, Mark S. / Effects of ribavirin dose reduction vs erythropoietin for boceprevir-related anemia in patients with chronic hepatitis C virus genotype 1 infection - A randomized trial. In: Gastroenterology. 2013 ; Vol. 145, No. 5.
@article{08e926612354452a92a34af36e59a5aa,
title = "Effects of ribavirin dose reduction vs erythropoietin for boceprevir-related anemia in patients with chronic hepatitis C virus genotype 1 infection - A randomized trial",
abstract = "Background & Aims Treatment of hepatitis C virus (HCV) infection with boceprevir, peginterferon, and ribavirin can lead to anemia, which has been managed by reducing ribavirin dose and/or erythropoietin therapy. We assessed the effects of these anemia management strategies on rates of sustained virologic response (SVR) and safety. Methods Patients (n = 687) received 4 weeks of peginterferon and ribavirin followed by 24 or 44 weeks of boceprevir (800 mg, 3 times each day) plus peginterferon and ribavirin. Patients who became anemic (levels of hemoglobin approximately ≤10 g/dL) during the study treatment period (n = 500) were assigned to groups that were managed by ribavirin dosage reduction (n = 249) or erythropoietin therapy (n = 251). Results Rates of SVR were comparable between patients whose anemia was managed by ribavirin dosage reduction (71.5{\%}) vs erythropoietin therapy (70.9{\%}), regardless of the timing of the first intervention to manage anemia or the magnitude of ribavirin dosage reduction. There was a threshold for the effect on rate of SVR: patients who received <50{\%} of the total milligrams of ribavirin assigned by the protocol had a significantly lower rate of SVR (P <.0001) than those who received ≥50{\%}. Among patients who did not develop anemia, the rate of SVR was 40.1{\%}. Eleven thromboembolic adverse events were reported in 9 of 295 patients who received erythropoietin, compared with 1 of 392 patients who did not receive erythropoietin. Conclusions Reduction of ribavirin dosage can be the primary approach for management of anemia in patients receiving peginterferon, ribavirin, and boceprevir for HCV infection. Reduction in ribavirin dosage throughout the course of triple therapy does not affect rates of SVR. However, it is important that the patient receives at least 50{\%} of the total amount (milligrams) of ribavirin assigned by response-guided therapy. ClinicalTrials.gov number, NCT01023035.",
keywords = "DAA, EPO, Erythropoiesis, Side Effect",
author = "Fred Poordad and Eric Lawitz and Reddy, {K. Rajender} and Afdhal, {Nezam H.} and Christophe H{\'e}zode and Stefan Zeuzem and Lee, {Samuel S.} and Calleja, {Jose Luis} and Brown, {Robert S.} and Antonio Craxi and Heiner Wedemeyer and Lisa Nyberg and Nelson, {David R.} and Lorenzo Rossaro and Luis Balart and Morgan, {Timothy R.} and Bacon, {Bruce R.} and Flamm, {Steven L.} and Kowdley, {Kris V.} and Weiping Deng and Koury, {Kenneth J.} and Pedicone, {Lisa D.} and Dutko, {Frank J.} and Burroughs, {Margaret H.} and Katia Alves and Janice Wahl and Brass, {Clifford A.} and Albrecht, {Janice K.} and Sulkowski, {Mark S.}",
year = "2013",
month = "11",
doi = "10.1053/j.gastro.2013.07.051",
language = "English (US)",
volume = "145",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "5",

}

TY - JOUR

T1 - Effects of ribavirin dose reduction vs erythropoietin for boceprevir-related anemia in patients with chronic hepatitis C virus genotype 1 infection - A randomized trial

AU - Poordad, Fred

AU - Lawitz, Eric

AU - Reddy, K. Rajender

AU - Afdhal, Nezam H.

AU - Hézode, Christophe

AU - Zeuzem, Stefan

AU - Lee, Samuel S.

AU - Calleja, Jose Luis

AU - Brown, Robert S.

AU - Craxi, Antonio

AU - Wedemeyer, Heiner

AU - Nyberg, Lisa

AU - Nelson, David R.

AU - Rossaro, Lorenzo

AU - Balart, Luis

AU - Morgan, Timothy R.

AU - Bacon, Bruce R.

AU - Flamm, Steven L.

AU - Kowdley, Kris V.

AU - Deng, Weiping

AU - Koury, Kenneth J.

AU - Pedicone, Lisa D.

AU - Dutko, Frank J.

AU - Burroughs, Margaret H.

AU - Alves, Katia

AU - Wahl, Janice

AU - Brass, Clifford A.

AU - Albrecht, Janice K.

AU - Sulkowski, Mark S.

PY - 2013/11

Y1 - 2013/11

N2 - Background & Aims Treatment of hepatitis C virus (HCV) infection with boceprevir, peginterferon, and ribavirin can lead to anemia, which has been managed by reducing ribavirin dose and/or erythropoietin therapy. We assessed the effects of these anemia management strategies on rates of sustained virologic response (SVR) and safety. Methods Patients (n = 687) received 4 weeks of peginterferon and ribavirin followed by 24 or 44 weeks of boceprevir (800 mg, 3 times each day) plus peginterferon and ribavirin. Patients who became anemic (levels of hemoglobin approximately ≤10 g/dL) during the study treatment period (n = 500) were assigned to groups that were managed by ribavirin dosage reduction (n = 249) or erythropoietin therapy (n = 251). Results Rates of SVR were comparable between patients whose anemia was managed by ribavirin dosage reduction (71.5%) vs erythropoietin therapy (70.9%), regardless of the timing of the first intervention to manage anemia or the magnitude of ribavirin dosage reduction. There was a threshold for the effect on rate of SVR: patients who received <50% of the total milligrams of ribavirin assigned by the protocol had a significantly lower rate of SVR (P <.0001) than those who received ≥50%. Among patients who did not develop anemia, the rate of SVR was 40.1%. Eleven thromboembolic adverse events were reported in 9 of 295 patients who received erythropoietin, compared with 1 of 392 patients who did not receive erythropoietin. Conclusions Reduction of ribavirin dosage can be the primary approach for management of anemia in patients receiving peginterferon, ribavirin, and boceprevir for HCV infection. Reduction in ribavirin dosage throughout the course of triple therapy does not affect rates of SVR. However, it is important that the patient receives at least 50% of the total amount (milligrams) of ribavirin assigned by response-guided therapy. ClinicalTrials.gov number, NCT01023035.

AB - Background & Aims Treatment of hepatitis C virus (HCV) infection with boceprevir, peginterferon, and ribavirin can lead to anemia, which has been managed by reducing ribavirin dose and/or erythropoietin therapy. We assessed the effects of these anemia management strategies on rates of sustained virologic response (SVR) and safety. Methods Patients (n = 687) received 4 weeks of peginterferon and ribavirin followed by 24 or 44 weeks of boceprevir (800 mg, 3 times each day) plus peginterferon and ribavirin. Patients who became anemic (levels of hemoglobin approximately ≤10 g/dL) during the study treatment period (n = 500) were assigned to groups that were managed by ribavirin dosage reduction (n = 249) or erythropoietin therapy (n = 251). Results Rates of SVR were comparable between patients whose anemia was managed by ribavirin dosage reduction (71.5%) vs erythropoietin therapy (70.9%), regardless of the timing of the first intervention to manage anemia or the magnitude of ribavirin dosage reduction. There was a threshold for the effect on rate of SVR: patients who received <50% of the total milligrams of ribavirin assigned by the protocol had a significantly lower rate of SVR (P <.0001) than those who received ≥50%. Among patients who did not develop anemia, the rate of SVR was 40.1%. Eleven thromboembolic adverse events were reported in 9 of 295 patients who received erythropoietin, compared with 1 of 392 patients who did not receive erythropoietin. Conclusions Reduction of ribavirin dosage can be the primary approach for management of anemia in patients receiving peginterferon, ribavirin, and boceprevir for HCV infection. Reduction in ribavirin dosage throughout the course of triple therapy does not affect rates of SVR. However, it is important that the patient receives at least 50% of the total amount (milligrams) of ribavirin assigned by response-guided therapy. ClinicalTrials.gov number, NCT01023035.

KW - DAA

KW - EPO

KW - Erythropoiesis

KW - Side Effect

UR - http://www.scopus.com/inward/record.url?scp=84886803976&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886803976&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2013.07.051

DO - 10.1053/j.gastro.2013.07.051

M3 - Article

C2 - 23924660

AN - SCOPUS:84886803976

VL - 145

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 5

ER -