van Vollenhoven Ronald F, Stohl William, Furie Richard A, Fox Norma Lynn, Groark James G, Bass Damon, Kurtinecz Milena, Pobiner Bonnie F, Eastman William J, Gonzalez-Rivera Tania, Gordon David
Department of Rheumatology, Amsterdam Rheumatology and Immunology Center ARC, Amsterdam, The Netherlands.
University of Southern California Keck School of Medicine, Los Angeles, California, USA.
Lupus Sci Med. 2018 Nov 26;5(1):e000288. doi: 10.1136/lupus-2018-000288. eCollection 2018.
The Systemic Lupus Erythematosus (SLE) Responder Index (SRI), developed as a primary outcome measure for use in clinical trials, captures improvement in SLE disease activity without concomitant worsening in disease manifestations. This study investigated the relationships between the SRI and clinical/laboratory correlates of SRI response in patients with SLE.
This was a post-hoc analysis of the phase III, double-blind, placebo-controlled study of subcutaneous BeLimumab in Subjects with Systemic lupus erythematosus - SubCutaneous (BLISS-SC). Patients were randomised to weekly belimumab 200 mg subcutaneously or placebo, plus standard SLE therapy. Changes from baseline to week 52 in clinical and laboratory parameters were compared among SRI responders and non-responders, irrespective of the treatment received.
SRI responders (n=475) had significantly better (p<0.0001) outcomes compared with non-responders (n=358), including (by definition) higher proportions achieving ≥4-point improvement in Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (100.0% vs 2.0%), no worsening in British Isles Lupus Assessment Group (BILAG; 0 new BILAG A or ≤1 new BILAG B score; 100.0 % vs 50.3%) and no worsening (<0.3-point increase) in Physician's Global Assessment score (100.0% vs 49.7%). Among patients receiving >7.5 mg/day corticosteroids at baseline, significantly more SRI responders had reductions in prednisone dose to ≤7.5 mg/day than non-responders. SRI responders reported lower flare rates and improvements in serological markers and Functional Assessment of Chronic Illness Therapy-Fatigue score than non-responders.
SRI response is associated with improvements in clinical and laboratory measures, strengthening its value as a clinically meaningful primary endpoint in clinical trials.
系统性红斑狼疮（SLE）反应指数（SRI）作为临床试验中的主要结局指标，用于评估SLE疾病活动度的改善情况，且不会伴随疾病表现的恶化。本研究调查了SLE患者中SRI与SRI反应的临床/实验室相关因素之间的关系。
这是一项对皮下注射贝利尤单抗治疗系统性红斑狼疮皮下给药（BLISS-SC）的III期双盲、安慰剂对照研究的事后分析。患者被随机分为皮下注射每周200mg贝利尤单抗组或安慰剂组，加标准SLE治疗。比较SRI反应者和无反应者从基线到第52周临床和实验室参数的变化，无论接受何种治疗。
与无反应者（n=358）相比，SRI反应者（n=475）的结局显著更好（p<0.0001），包括（根据定义）在《狼疮性红斑中雌激素安全性全国评估-SLE疾病活动指数》中达到≥4分改善的比例更高（100.0%对2.0%），英国狼疮评估组（BILAG）无恶化（0个新的BILAG A或≤1个新的BILAG B评分；100.0%对50.3%），医生整体评估评分无恶化（增加<0.3分；100.0%对49.7%）。在基线时接受>7.5mg/天皮质类固醇治疗的患者中，与无反应者相比，显著更多的SRI反应者将泼尼松剂量降至≤7.5mg/天。与无反应者相比，SRI反应者报告的疾病发作率更低，血清学指标和慢性病治疗功能评估-疲劳评分有所改善。
SRI反应与临床和实验室指标的改善相关，强化了其作为临床试验中具有临床意义的主要终点的价值。
