Anemia during treatment with peginterferon Alfa-2b/ribavirin and boceprevir: Analysis from the serine protease inhibitor therapy 2 (SPRINT-2) trial.
Boceprevir (BOC) added to peginterferon alfa-2b (PegIFN) and ribavirin (RBV) significantly increases sustained virologic response (SVR) rates over PegIFN/RBV alone in previously untreated adults with chronic hepatitis C genotype 1. We evaluate the relationship of incident anemia with triple therapy. A total of 1,097 patients received a 4-week lead-in of PegIFN/RBV followed by: (1) placebo plus PegIFN/RBV for 44 weeks (PR48); (2) BOC plus PegIFN/RBV using response-guided therapy (BOC/RGT); and (3) BOC plus PegIFN/RBV for 44 weeks (BOC/PR48). The management of anemia (hemoglobin [Hb]<10 g/dL) included RBV dose reduction and/or erythropoietin (EPO) use. A total of 1,080 patients had ≥1 Hb measurement during treatment. The incidence of anemia was 50% in the BOC arms combined (363/726) and 31% in the PR48 arm (108/354, P<0.001). Among BOC recipients, lower baseline Hb and creatinine clearance were associated with incident anemia. In the BOC-containing arms, anemia was managed by the site investigators as follows: EPO without RBV dose reduction, 38%; RBV dose reduction without EPO, 8%; EPO with RBV dose reduction, 40%; and neither RBV dose reduction nor EPO, 14%. SVR rates were not significantly affected by management strategy (70%-74%), and overall patients with anemia had higher rates of SVR than those who did not develop anemia (58%). Serious and life-threatening adverse events (AEs) and discontinuations due to AEs among BOC-treated patients did not differ by EPO use.


CONCLUSIONS
With BOC/PR therapy, SVR rates in patients with incident anemia were higher than nonanemic patients and did not vary significantly according to the investigator-selected approach for anemia management. Prospective studies are needed to confirm this observation.
Johns Hopkins University School of Medicine, Baltimore, MD 21287-0003, USA. msulkowski@jhmi.edu
Mark S
MS
Sulkowski
Fred
F
Poordad
Michael P
MP
Manns
Jean-Pierre
JP
Bronowicki
K
K
Rajender Reddy
Stephen A
SA
Harrison
Nezam H
NH
Afdhal
Heather L
HL
Sings
Lisa D
LD
Pedicone
Kenneth J
KJ
Koury
Vilma
V
Sniukiene
Margaret H
MH
Burroughs
Janice K
JK
Albrecht
Clifford A
CA
Brass
Ira M
IM
Jacobson
D000328:Adult; D000740:Anemia / Q000139:chemically induced* / Q000188:drug therapy; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006397:Hematinics / Q000008:administration & dosage / Q000009:adverse effects; D006454:Hemoglobins / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D010919:Placebos; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects*; D011392:Proline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects*; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
D000998:Antiviral Agents; D006397:Hematinics; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010919:Placebos; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; 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