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June 24, 2005 —A short course
of hormone therapy (HT) is associated with a small risk of flare
of systemic lupus erythematosus (SLE), according to the results
of a randomized, double-blind trial published in the June 21 issue
of the Annals of Internal Medicine.
"There is concern that exogenous female hormones may worsen disease
activity in women with SLE," write Jill P. Buyon, MD, from the
Hospital for Joint Diseases of New York University School of Medicine,
and colleagues. "However, health issues specific to women warrant
attention and need to be confronted in patients with SLE. Although
long-term HRT is not currently recommended, short-term salutary
effects include treatment of hot flashes and vaginal dryness."
The Safety of Estrogens in Lupus Erythematosus, National Assessment
(SELENA) trial consisted of two separate randomized, placebo-controlled,
multicenter studies, including the trial of HT vs placebo reported
here. This noninferiority trial conducted from March 1996 to June
2002 was designed to determine the effect of conjugated estrogens
and cyclic progestins on disease activity in postmenopausal women
with SLE.
At 16 university-affiliated rheumatology clinics or practices
in 11 U.S. states, 351 menopausal patients were randomized to 12
months of treatment with active drug (0.625 mg of conjugated estrogen
daily, plus 5 mg of medroxyprogesterone for 12 days per month)
or placebo. Mean age was 50 years; 81.5% had inactive and 18.5%
had stable SLE.
Follow-up rate at 12 months was 82% for the HT group and 87% for
the placebo group, and the primary endpoint was occurrence of a
severe flare as defined by SELENA–SLE Disease Activity Index
composite.
During the 12-month study, the severe flare rate was 0.081 for
HT and 0.049 for placebo (estimated difference, 0.033; P =
.23; upper limit of the one-sided 95% confidence interval for the
treatment difference, 0.078, which was within the prespecified
margin of 9% for noninferiority).
Mild to moderate flare rates were 1.14 flares per person-year
for HT and 0.86 flare per person-year for placebo (relative risk,
1.34; P = .01). The probability of any type of flare by
12 months was 0.64 with HT and 0.51 with placebo (P = .01).
In the HT group, one patient died, one had a stroke, two had deep
venous thrombosis, and one developed thrombosis in an arteriovenous
graft. In the placebo group, one patient developed deep venous
thrombosis.
Study limitations are lack of generalizability to women with high-titer
anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis.
"Adding a short course of HRT is associated with a small risk
for increasing the natural flare rate of lupus," the authors write. "Most
of these flares are mild to moderate. The benefits of HRT can be
balanced against the risk for flare because HRT did not significantly
increase the risk for severe flare compared with placebo."
The National Institute of Arthritis and Musculoskeletal and Skin
Diseases, an agency of the National Institutes of Health, supported
this study. Wyeth-Ayerst Pharmaceuticals provided the study drug
(Premarin or cyclic Provera) and matching placebo without cost.
The authors report no potential financial conflicts of interest.
Ann Intern Med. 2005;142:953-962
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