Published in Journal Watch Gastroenterology December 14, 2012
Adding raloxifene hydrochloride to standard therapy significantly increased response, but only among women with IL28B genotype TT.
Studies of hepatitis C virus (HCV) infection treatment have shown that response to interferon-based therapy is lower in postmenopausal women than in premenopausal women. This could be caused by declining estrogen levels in menopause. To test that hypothesis, investigators evaluated whether the addition of raloxifene hydrochloride (RLX) — a selective estrogen receptor modulator — improved the efficacy of standard therapy with peginterferon and ribavirin in this group.
Investigators randomized 123 postmenopausal Japanese women aged 50 to 73 years with genotype 1b HCV infection to receive 60 mg of RLX daily plus standard therapy with 180 µg of peginterferon weekly and 600 to 1000 µg of ribavirin daily or standard therapy only for 48 weeks. The primary end point was sustained virologic response (SVR), defined as undetectable serum HCV RNA after 24 weeks of treatment. The mean length of time since menopause was 10.2 years (range, 2–22 years). Baseline characteristics of the two groups did not differ.
SVR was significantly higher in the RLX group than the standard therapy group overall (61.3% vs. 34.4%; P=0.005) and in a subgroup with IL28B genotype TT (72.5% vs. 39.2%; P=0.001), but not in patients with IL28B genotype CC or TC. Only one patient discontinued RLX after developing a rash during week 2 of treatment.
Comment: These results suggest that the addition of RLX as adjuvant therapy to peginterferon and ribavirin in postmenopausal women with genotype 1b HCV infection significantly improves SVR. The improvement was limited to women with IL28B genotype TT. The mechanism by which RLX improves SVR is unclear but could involve the improvement of estradiol levels and reduction of oxidative stress or inhibition of inflammatory cytokine production. Regardless, further study of the use of RLX and other, similar agents as adjuvant therapy to HCV regimens is warranted.
Furusyo N et al. Raloxifene hydrochloride is an adjuvant antiviral treatment of postmenopausal women with chronic hepatitis C: A randomized trial. J Hepatol 2012 Dec; 57:1186. (http://dx.doi.org/10.1016/j.jhep.2012.08.003)
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