Morand Eric F, Furie Richard A, Bruce Ian N, Vital Edward M, Dall'Era Maria, Maho Emmanuelle, Pineda Lilia, Tummala Raj
Centre for Inflammatory Disease, Monash University, Melbourne, VIC, Australia.
Division of Rheumatology, Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA.
Lancet Rheumatol. 2022 Apr;4(4):e282-e292. doi: 10.1016/S2665-9913(21)00317-9. Epub 2022 Feb 3.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by multisystem involvement. We aimed to evaluate the efficacy of anifrolumab on organ domain-specific SLE disease activity.
In this post-hoc analysis, data were pooled from the randomised, placebo-controlled, phase 3 TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) trials of anifrolumab (300 mg intravenously once every 4 weeks for 48 weeks) in patients aged 18-70 years with moderate-to-severe SLE. We evaluated changes from baseline to week 52 in British Isles Lupus Assessment Group 2004 (BILAG-2004) and SLE Disease Activity Index 2000 (SLEDAI-2K) organ domain scores, Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score (CLASI-A), swollen and tender joint counts, haematology, and serology.
Among the 726 patients included, the mean age was 41·8 years (SD 11·9); 674 (93%) were female, 52 (7%) were male, and 479 (66%) were White. 360 patients received anifrolumab 300 mg (180 patients in each trial), and 366 received placebo (184 patients in TULIP-1 and 182 patients in TULIP-2). The most frequently affected organ domains at baseline were musculoskeletal (645 [89%] patients based on BILAG-2004; 684 [94%] with SLEDAI-2K) and mucocutaneous (627 [86%] with BILAG-2004; 699 [96%] based on SLEDAI-2K). At week 52, anifrolumab treatment resulted in greater improvements versus placebo in the musculoskeletal system (176 [56%] of 317 patients vs 143 [44%] of 328 with BILAG-2004; 164 [49%] of 335 vs 141 [40%] of 349 with SLEDAI-2K), the mucocutaneous system (168 [54%] of 315 vs 119 [38%] of 312 with BILAG-2004; 190 [55%] of 348 vs 138 [39%] of 351 SLEDAI-2K), and immunological system (44 [19%] of 237 vs 26 [11%] of 230 with SLEDAI-2K). Less frequently affected domains had varied responses. Among patients with a CLASI-A of 10 or more at baseline, greater proportions of patients receiving anifrolumab than placebo achieved a reduction of 50% or more in CLASI-A at week 52 (49 [46%] of 107 vs 24 [25%] of 94). Among patients with at least six swollen joints, more patients in the anifrolumab group than in the placebo group had a 50% or more reduction from baseline to week 52 in swollen joint count (99 [57%] of 174 vs 92 [46%] of 200), but the difference between groups was not significant for 50% or more reduction in tender joint count.
Across the two pivotal phase 3 trials, anifrolumab treatment improved SLE disease activity across multiple organ domains.
AstraZeneca.
系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，其特征为多系统受累。我们旨在评估阿尼鲁单抗对器官领域特异性SLE疾病活动的疗效。
在这项事后分析中，数据汇集自阿尼鲁单抗（每4周静脉注射300mg，共48周）针对18至70岁中重度SLE患者进行的随机、安慰剂对照3期TULIP-1（NCT02446912）和TULIP-2（NCT02446899）试验。我们评估了从基线到第52周英国狼疮评估组2004（BILAG-2004）和SLE疾病活动指数2000（SLEDAI-2K）器官领域评分、皮肤红斑狼疮疾病面积和严重程度指数活动评分（CLASI-A）、肿胀和压痛关节计数、血液学及血清学的变化。
纳入的726例患者中，平均年龄为41.8岁（标准差11.9）；674例（93%）为女性，52例（7%）为男性，479例（66%）为白人。360例患者接受阿尼鲁单抗300mg（每项试验180例），366例接受安慰剂（TULIP-1中184例，TULIP-2中182例）。基线时最常受累的器官领域为肌肉骨骼（基于BILAG-2004为645例[89%]患者；基于SLEDAI-2K为684例[94%]）和黏膜皮肤（基于BILAG-2004为627例[86%]；基于SLEDAI-2K为699例[96%]）。在第52周，与安慰剂相比，阿尼鲁单抗治疗使肌肉骨骼系统（基于BILAG-2004，317例患者中的176例[56%] vs 328例中的143例[44%]；基于SLEDAI-2K，335例中的164例[49%] vs 349例中的141例[40%]）、黏膜皮肤系统（基于BILAG-2004，315例中的168例[54%] vs 312例中的119例[38%]；基于SLEDAI-2K，348例中的190例[55%] vs 351例中的138例[39%]）和免疫系统（基于SLEDAI-2K，237例中的44例[19%] vs 230例中的26例[11%]）有更大改善。较少受累的领域有不同反应。在基线时CLASI-A为10或更高的患者中，在第52周接受阿尼鲁单抗的患者中CLASI-A降低50%或更多的比例高于接受安慰剂的患者（107例中的49例[46%] vs 94例中的24例[25%]）。在至少有6个肿胀关节的患者中，从基线到第52周，阿尼鲁单抗组肿胀关节计数减少50%或更多的患者多于安慰剂组（174例中的99例[57%] vs 200例中的92例[46%]），但两组间压痛关节计数减少50%或更多的差异不显著。
在两项关键的3期试验中，阿尼鲁单抗治疗改善了多个器官领域的SLE疾病活动。
阿斯利康公司。
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