Raloxifene hydrochloride is an adjuvant antiviral treatment of postmenopausal women with chronic hepatitis C: a randomized trial.
OBJECTIVE
Early menopause in women with chronic hepatitis C virus (HCV) infection is associated with a low likelihood of a sustained virological response (SVR) in conjunction with their antiviral treatment. This is potentially related to their reduced estrogen secretion. The study was done to determine whether selective estrogen receptor modulator administration might improve the efficacy of the current standard of care (SOC) treatment, pegylated interferon (PegIFN) α2a plus ribavirin (RBV), for postmenopausal women.


METHODS
One hundred and twenty-three postmenopausal women with genotype 1b chronic hepatitis C were randomly assigned to one of two treatment groups: raloxifene hydrochloride (RLX) (60 mg/day) plus SOC (PegIFNα2a 180 μg/week and RBV 600-1,000 mg/day) (n=62) or SOC only (n=61). Genotyping was performed of the polymorphism in the interleukin-28B (IL28B) gene region (rs8099917) of DNA collected from each patient.


RESULTS
One RLX-treated patient discontinued RLX because of a systemic rash following 2 weeks of treatment. Twenty-four weeks after treatment, the SVR rate was significantly higher for RLX plus SOC patients (61.3%) than for SOC only patients (34.4%) (p=0.0051). Further, the SVR rate was significantly higher for RLX plus SOC patients with IL28B TT (72.5%) than for SOC only patients with IL28B TT (39.2%) (p=0.0014), but no such relationship was observed in patients carrying the minor IL28B allele.


CONCLUSIONS
RLX improved the efficacy of SOC in the treatment of postmenopausal women with chronic hepatitis C. RLX shows promise as an adjuvant to the standard antiviral treatment of such patients.
Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
Norihiro
N
Furusyo
Eiichi
E
Ogawa
Masayuki
M
Sudoh
Masayuki
M
Murata
Takeshi
T
Ihara
Takeo
T
Hayashi
Hiroaki
H
Ikezaki
Satoshi
S
Hiramine
Haru
H
Mukae
Kazuhiro
K
Toyoda
Hiroaki
H
Taniai
Kyoko
K
Okada
Mosaburo
M
Kainuma
Eiji
E
Kajiwara
Jun
J
Hayashi
D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use*; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D017698:Postmenopause; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D000095022:Interferon Lambda
D000277:Adjuvants, Pharmaceutic; D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D020849:Raloxifene Hydrochloride; D011994:Recombinant Proteins; D012254:Ribavirin; D020845:Selective Estrogen Receptor Modulators; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a