High-dose cyclophosphamide versus monthly intravenous cyclophosphamide for systemic lupus erythematosus: a prospective randomized trial.

OBJECTIVE: Monthly intravenous (IV) cyclophosphamide for 6 months has been the standard induction regimen for lupus nephritis, followed by a maintenance regimen of quarterly infusions for 2 years. We undertook this study to compare the efficacy and safety of the standard regimen versus a high-dose IV cyclophosphamide regimen. METHODS: We performed a prospective randomized trial comparing monthly IV cyclophosphamide at 750 mg/m(2) body surface area for 6 months followed by quarterly IV cyclophosphamide for 2 years (traditional treatment) against high-dose IV cyclophosphamide (50 mg/kg daily for 4 days) (high-dose treatment). Entry criteria included renal lupus, neurologic lupus, or other organ system involvement with moderate-to-severe activity. RESULTS: Fifty-one patients were randomized; 3 withdrew before treatment and 1 committed suicide after 2 months of high-dose treatment. Twenty-two had renal lupus, 14 had neurologic lupus, and 11 had other organ involvement. The outcome measure was the Responder Index for Lupus Erythematosus (complete response, partial response, no change, or worsening). At 6 months (the end of induction), 11 of 21 patients (52%) in the high-dose treatment group had a complete response compared with 9 of 26 patients (35%) in the traditional treatment group (P = 0.13). At the final visit (30 months), 10 of 21 patients (48%) in the high-dose treatment group had a complete response compared with 13 of 20 patients (65%) who continued with traditional treatment (P = 0.13). Six patients crossed over from traditional treatment to high-dose treatment because of lack of response, and 3 of those patients became complete responders. CONCLUSION: There was not strong evidence that monthly IV cyclophosphamide and high-dose IV cyclophosphamide differed in complete or in any (complete or partial) response to induction or maintenance therapy. However, nonresponders to monthly IV cyclophosphamide can sometimes be rescued with high-dose IV cyclophosphamide.

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.