系统性红斑狼疮诊治进展.pptVIP

艾拉莫德可改善MRL/lpr免疫性肾炎。雌性MRL/lpr小鼠，自第8周龄起给予艾拉莫德 30mg/kg·d（n=14）或空白载体溶液（n=16）。 (A) 小鼠蛋白尿水平。 (B) 第28周处死所有小鼠观察肾脏病理。艾拉莫德治疗后小鼠肾组织，大致正常；安慰剂组小鼠肾脏，可见新月体、小球硬化（星号）、间质炎症细胞浸润及管型等多种病变。 （C）小鼠肾脏病理评分 (D)MRL/lpr小鼠，自第8周龄起给予艾拉莫德30mg/kg·d或空白载体溶液。艾拉莫德可降低小鼠血清抗dsDNA抗体滴度。 (E)艾拉莫德在给药12w后可显著降低MRL/lpr小鼠血清各亚型免疫球蛋白水平，与阳性对照药物环磷酰胺（Cyc）作用接近。 ? * Abstract Objective To assess the efficacy and safety of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE). Methods Patients with moderate-to-severe SLE (SELENA-SLEDAI ≥8) were randomized (2:1) to weekly belimumab 200 mg SC or placebo by prefilled syringe, plus standard SLE therapy (SoC), for 52 weeks. Primary endpoint was SLE Responder Index (SRI4) at Week 52. Secondary endpoints were time to severe flare and reduction in corticosteroid dose. Safety was assessed by adverse event (AE) reporting and laboratory testing. Results Of 839 patients randomized, 836 (556 belimumab/280 placebo) received treatment; 159 withdrew. At entry, mean SELENA-SLEDAI scores were 10.5 (belimumab) and 10.3 (placebo). More patients who received belimumab were SRI4 responders than those who received placebo (61.4% vs 48.4%; odds ratio [OR] [95% CI]: 1.68 [1.25, 2.25]; p=0.0006). In the belimumab group, time to and risk of severe flare were improved (median 171.0 versus 118.0 days; HR [95% CI]: 0.51 [0.35, 0.74]; p=0.0004), and more patients reduced corticosteroid dose by ≥25% to ≤7.5 mg/day during Weeks 40-52 (18.2% vs 11.9%; OR [95% CI]: 1.65 [0.95, 2.84]; p=0.0732), compared with placebo. AE incidence was comparable between treatment groups; serious AEs were reported for 10.8% (belimumab) and 15.7% (placebo) of patients. Hypoglobulinemia immunoglobulin G worsening by ≥2 grades occurred in 0.9% (belimumab) and 1.4% (placebo) of patients. Conclusion In patients with moderate-to-severe SLE, weekly belimumab 200 mg SC plus SoC significantly improved SRI4 response, decreased severe flare compared with placebo, and had a safety profile similar t