Manzi Susan, Sánchez-Guerrero Jorge, Yokogawa Naoto, Wenzel Joerg, Ocran-Appiah Josephine C, Harris Julia Hn, Khamashta Munther, Rubin Bernard, Lynn Fox Norma, Levy Roger A, Werth Victoria P
Allegheny Health Network, Lupus Center of Excellence, Pittsburgh, PA, USA.
Division of Rheumatology, Department of Medicine Mount Sinai Hospital/University Health Network, University of Toronto, Toronto, ON, Canada.
Lupus. 2025 Jun;34(7):666-678. doi: 10.1177/09612033251337130. Epub 2025 May 5.
ObjectiveTo investigate the effects of belimumab (BEL) on systemic lupus erythematosus (SLE) mucocutaneous and vasculitis manifestations.MethodsThis post hoc, integrated Belimumab Summary of Lupus Efficacy (Be-SLE) analysis pooled data from five international Phase 3, randomized, placebo (PBO)-controlled BEL trials (BLISS-52 [NCT00424476; conducted in 2007-2009], BLISS-76 [NCT00410384; 2007-2009], BLISS-SC [NCT01484496; 2011-2015], North East Asia [NCT01345253; 2011-2015], EMBRACE [NCT01632241; 2013-2018]). Adults with active SLE and Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥6 (BLISS-52, BLISS-76) or ≥8 (BLISS-SC, North East Asia, EMBRACE), randomized to BEL (10 mg/kg/month intravenously or 200 mg/week subcutaneously) or PBO, plus standard therapy (ST) were included. Mucocutaneous and vasculitis manifestations (listed below) were measured (baseline and every 4 weeks) for 52 weeks using SELENA-SLEDAI and British Isles Lupus Assessment Group (BILAG).ResultsOf 3086 patients (BEL, = 1869; PBO, = 1217), 85% (BEL and PBO) by SELENA-SLEDAI and 58% (BEL) and 62% (PBO) by BILAG (moderate or severe activity) had mucocutaneous manifestations, and <10% had vasculitis at baseline. At Week 52, significantly more BEL-treated than PBO-treated patients demonstrated improvements in SELENA-SLEDAI (59% vs 49%; < .0001) and BILAG (54% vs 43%; < .0001) mucocutaneous domains. Significant differences between-treatment favored BEL at Week 52 for resolution of all SELENA-SLEDAI items (vasculitis, rash, alopecia, and mucosal ulcers), and nine of 20 BILAG items (mild maculopapular eruption, localized active discoid lesions, mild alopecia, small mucosal ulceration, malar erythema, subcutaneous nodules, swollen fingers, major cutaneous vasculitis including ulcers, and minor cutaneous vasculitis).ConclusionPatients with SLE treated with BEL plus ST experienced significant improvements in most mucocutaneous and vasculitis manifestations compared with patients receiving PBO plus ST. These data provide additional support for the use of BEL in SLE and show that it is associated with skin improvements.
目的
研究贝利尤单抗（BEL）对系统性红斑狼疮（SLE）皮肤黏膜及血管炎表现的影响。
方法
这项事后综合的贝利尤单抗狼疮疗效总结（Be-SLE）分析汇总了五项国际3期随机、安慰剂（PBO）对照的BEL试验（BLISS-52 [NCT00424476；2007 - 2009年开展]、BLISS-76 [NCT00410384；2007 - 2009年]、BLISS-SC [NCT01484496；2011 - 2015年]、东北亚 [NCT01345253；2011 - 2015年]、EMBRACE [NCT01632241；2013 - 2018年]）的数据。纳入有活动性SLE且系统性红斑狼疮疾病活动指数（SELENA-SLEDAI）评分≥6（BLISS-52、BLISS-76）或≥8（BLISS-SC、东北亚、EMBRACE）的成年人，随机分为接受BEL（静脉注射10 mg/kg/月或皮下注射200 mg/周）或PBO，并联合标准治疗（ST）。使用SELENA-SLEDAI和不列颠群岛狼疮评估组（BILAG）在52周内（基线及每4周一次）测量皮肤黏膜及血管炎表现（如下所列）。
结果
在3086例患者中（BEL组1869例；PBO组1217例），根据SELENA-SLEDAI评估85%（BEL组和PBO组）有皮肤黏膜表现，根据BILAG评估（中度或重度活动）BEL组为58%、PBO组为62%有皮肤黏膜表现，且基线时<10%有血管炎。在第52周时，接受BEL治疗的患者在SELENA-SLEDAI（59% vs 49%；P<0.0001）和BILAG（54% vs 43%；P<0.0001）皮肤黏膜领域的改善明显多于接受PBO治疗的患者。在第52周时，治疗组间在所有SELENA-SLEDAI项目（血管炎皮疹、脱发和黏膜溃疡）的缓解以及20项BILAG项目中的9项（轻度斑丘疹、局限性活动性盘状皮损、轻度脱发、小黏膜溃疡、颧部红斑、皮下结节、手指肿胀、包括溃疡的主要皮肤血管炎和轻度皮肤血管炎）方面的差异均有利于BEL组。
结论
与接受PBO联合ST治疗的患者相比，接受BEL联合ST治疗的SLE患者在大多数皮肤黏膜及血管炎表现方面有显著改善。这些数据为BEL在SLE中的应用提供了额外支持，并表明其与皮肤改善相关。
