Effects of ribavirin dose reduction vs erythropoietin for boceprevir-related anemia in patients with chronic hepatitis C virus genotype 1 infection--a randomized trial.
OBJECTIVE
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.
Texas Liver Institute/University of Texas Health Science Center, San Antonio, Texas. Electronic address: poordad@txliver.com.
Fred
F
Poordad
Eric
E
Lawitz
K Rajender
KR
Reddy
Nezam H
NH
Afdhal
Christophe
C
Hézode
Stefan
S
Zeuzem
Samuel S
SS
Lee
Jose Luis
JL
Calleja
Robert S
RS
Brown
Antonio
A
Craxi
Heiner
H
Wedemeyer
Lisa
L
Nyberg
David R
DR
Nelson
Lorenzo
L
Rossaro
Luis
L
Balart
Timothy R
TR
Morgan
Bruce R
BR
Bacon
Steven L
SL
Flamm
Kris V
KV
Kowdley
Weiping
W
Deng
Kenneth J
KJ
Koury
Lisa D
LD
Pedicone
Frank J
FJ
Dutko
Margaret H
MH
Burroughs
Katia
K
Alves
Janice
J
Wahl
Clifford A
CA
Brass
Janice K
JK
Albrecht
Mark S
MS
Sulkowski
D000465:Algorithms; D000740:Anemia / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D019468:Disease Management; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D004921:Erythropoietin; D011092:Polyethylene Glycols; D012254:Ribavirin; 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; C417083:peginterferon alfa-2b
CI; DAA; EPO; Erythropoiesis; HCV; RBV; SVR; Side Effect; confidence interval; erythropoietin; hepatitis C virus; ribavirin; sustained virologic response