系统性红斑狼疮女性使用复方口服避孕药的情况。

Combined oral contraceptives in women with systemic lupus erythematosus.

作者信息

Petri Michelle, Kim Mimi Y, Kalunian Kenneth C, Grossman Jennifer, Hahn Bevra H, Sammaritano Lisa R, Lockshin Michael, Merrill Joan T, Belmont H Michael, Askanase Anca D, McCune W Joseph, Hearth-Holmes Michelene, Dooley Mary Anne, Von Feldt Joan, Friedman Alan, Tan Mark, Davis John, Cronin Mary, Diamond Betty, Mackay Meggan, Sigler Lisa, Fillius Michael, Rupel Ann, Licciardi Frederick, Buyon Jill P

机构信息

Johns Hopkins University School of Medicine, Baltimore, USA.

出版信息

N Engl J Med. 2005 Dec 15;353(24):2550-8. doi: 10.1056/NEJMoa051135.

DOI:10.1056/NEJMoa051135

PMID:16354891

Abstract

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.

摘要

背景

由于担心潜在的负面副作用，系统性红斑狼疮女性很少被处方口服避孕药。在这项双盲、随机、非劣效性试验中，我们前瞻性评估了口服避孕药对绝经前系统性红斑狼疮女性狼疮活动的影响。

方法

在美国15个地点，共有183名系统性红斑狼疮病情处于非活动期（76%）或稳定活动期（24%）的女性被随机分配接受口服避孕药（三相炔雌醇，剂量为35微克，加炔诺酮，剂量为0.5至1毫克，共12个周期，每个周期28天；91名女性）或安慰剂（92名女性），并在第1、2、3、6、9和12个月进行评估。如果受试者抗心磷脂抗体水平为中度或高度、有狼疮抗凝物或有血栓形成病史，则被排除。

结果

主要终点，即严重狼疮发作，在接受口服避孕药的91名受试者中有7名发生（7.7%），而接受安慰剂的92名受试者中有7名发生（7.6%）。12个月时的严重发作率相似：接受口服避孕药组为0.084，安慰剂组为0.087（P = 0.95；该差异的单侧95%置信区间上限为0.069，在预先设定的9%非劣效性界限内）。接受口服避孕药的受试者轻度或中度发作率为每人每年1.40次发作，接受安慰剂的受试者为每人每年1.44次发作（相对风险，0.98；P = 0.86）。在随机接受口服避孕药的组中，有1例深静脉血栓形成和1例移植血管血栓形成；在安慰剂组中，有1例深静脉血栓形成、1例眼部血栓形成、1例浅表血栓性静脉炎和1例死亡（试验停止后）。