Combined oral contraceptives in women with systemic lupus erythematosus.
BACKGROUND
Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus.


METHODS
A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.S. sites were randomly assigned to receive either oral contraceptives (triphasic ethinyl estradiol at a dose of 35 microg plus norethindrone at a dose of 0.5 to 1 mg for 12 cycles of 28 days each; 91 women) or placebo (92 women) and were evaluated at months 1, 2, 3, 6, 9, and 12. Subjects were excluded if they had moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis.


RESULTS
The primary end point, a severe lupus flare, occurred in 7 of 91 subjects receiving oral contraceptives (7.7 percent) as compared with 7 of 92 subjects receiving placebo (7.6 percent). The 12-month rates of severe flare were similar: 0.084 for the group receiving oral contraceptives and 0.087 for the placebo group (P=0.95; upper limit of the one-sided 95 percent confidence interval for this difference, 0.069, which is within the prespecified 9 percent margin for noninferiority). Rates of mild or moderate flares were 1.40 flares per person-year for subjects receiving oral contraceptives and 1.44 flares per person-year for subjects receiving placebo (relative risk, 0.98; P=0.86). In the group that was randomized to receive oral contraceptives, there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial).


CONCLUSIONS
Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable.
Petri
Michelle
M
Johns Hopkins University School of Medicine, Baltimore, USA.
Kim
Mimi Y
MY
Kalunian
Kenneth C
KC
Grossman
Jennifer
J
Hahn
Bevra H
BH
Sammaritano
Lisa R
LR
Lockshin
Michael
M
Merrill
Joan T
JT
Belmont
H Michael
HM
Askanase
Anca D
AD
McCune
W Joseph
WJ
Hearth-Holmes
Michelene
M
Dooley
Mary Anne
MA
Von Feldt
Joan
J
Friedman
Alan
A
Tan
Mark
M
Davis
John
J
Cronin
Mary
M
Diamond
Betty
B
Mackay
Meggan
M
Sigler
Lisa
L
Fillius
Michael
M
Rupel
Ann
A
Licciardi
Frederick
F
Buyon
Jill P
JP
D000293:Adolescent; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D004311:Double-Blind Method; D004997:Ethinyl Estradiol / Q000009:adverse effects; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000145:classification; D009640:Norethindrone / Q000009:adverse effects; D011247:Pregnancy; D012720:Severity of Illness Index
D003277:Contraceptives, Oral, Combined; D004997:Ethinyl Estradiol; D009640:Norethindrone