Faculty Bibliography

The antineutrophil cytoplasmic antibodies (ANCA)-associated small vessel vasculitides include Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis (MPA), and the renal limited form of MPA, also known as pauci-immune or idiopathic crescentic glomerulonephritis. ANCA are probably necessary but not sufficient for disease pathogenicity. Classical induction and maintenance therapy of these conditions with corticosteroids and long-term cyclophosphamide is associated with occasional relapse and major toxicities. Therefore, treatment regimens being investigated include induction with methotrexate or, especially for patients with more aggressive disease accompanied by renal insufficiency, therapies that include either pulses of methylprednisolone or plasma exchanges. Nontraditional options for maintenance therapy may include step-down treatment with azathioprine or mycophenolate mofetil. For patients with Wegener's granulomatosis, studies have shown a reduced occurrence of flares with the use of co-trimoxazole. Finally, although a carefully randomized controlled trial with etanercept demonstrated that this tumor necrosis factor (TNF)-blocking agent was not superior to conventional maintenance therapy, a biologic agent with a different mechanism of action, rituximab, may prove a satisfactory alternative

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

BACKGROUND: There is concern that exogenous female hormones may worsen disease activity in women with systemic lupus erythematosus (SLE). OBJECTIVE: To evaluate the effect of hormone replacement therapy (HRT) on disease activity in postmenopausal women with SLE. DESIGN: Randomized, double-blind, placebo-controlled noninferiority trial conducted from March 1996 to June 2002. SETTING: 16 university-affiliated rheumatology clinics or practices in 11 U.S. states. PATIENTS: 351 menopausal patients (mean age, 50 years) with inactive (81.5%) or stable-active (18.5%) SLE. Interventions: 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. The 12-month follow-up rate was 82% for the HRT group and 87% for the placebo group. MEASUREMENTS: The primary end point was occurrence of a severe flare as defined by Safety of Estrogens in Lupus Erythematosus, National Assessment-Systemic Lupus Erythematosus Disease Activity Index composite. RESULTS: Severe flare was rare in both treatment groups: The 12-month severe flare rate was 0.081 for the HRT group and 0.049 for the placebo group, yielding an estimated difference of 0.033 (P = 0.23). The upper limit of the 1-sided 95% CI for the treatment difference was 0.078, within the prespecified margin of 9% for noninferiority. Mild to moderate flares were significantly increased in the HRT group: 1.14 flares/person-year for HRT and 0.86 flare/person-year for placebo (relative risk, 1.34; P = 0.01). The probability of any type of flare by 12 months was 0.64 for the HRT group and 0.51 for the placebo group (P = 0.01). In the HRT group, there were 1 death, 1 stroke, 2 cases of deep venous thrombosis, and 1 case of thrombosis in an arteriovenous graft; in the placebo group, 1 patient developed deep venous thrombosis. LIMITATIONS: Findings are not generalizable to women with high-titer anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis. CONCLUSIONS: Adding a short course of HRT is associated with a small risk for increasing the natural flare rate of lupus. 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

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine. Agents that neutralize TNF-alpha are effective in the treatment of disorders such as rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), spondyloarthropathies, and inflammatory bowel disease. TNF-alpha antagonist therapy has been associated with the development of antinuclear antibodies (ANA) and double-stranded DNA (dsDNA) antibodies, as well as the infrequent development of systemic lupus erythematosus (SLE)-like disease. We describe the first case of biopsy-confirmed proliferative lupus nephritis and leukocytoclastic vasculitis in a patient treated with etanercept for JRA