McGill University and the Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
University of Calgary, Calgary, Alberta, Canada, and Arthritis Research Canada, Richmond, British Columbia, Canada.
Arthritis Rheumatol. 2018 Sep;70(9):1450-1458. doi: 10.1002/art.40522. Epub 2018 Aug 3.
Trials of new systemic lupus erythematosus (SLE) treatments are hampered by the lack of effective outcome measures. To address this, we developed a novel Lupus Multivariable Outcome Score (LuMOS) and assessed its performance using data from 2 randomized controlled trials of belimumab in patients with SLE.
The LuMOS formula was developed by analyzing raw data from 2 pivotal trials, the Study of Belimumab in Subjects with SLE 52-week (BLISS-52) and 76-week (BLISS-76) trials, which are the basis for approval of belimumab. Using the BLISS-76 trial data as the learning data set, we carried out multivariable logistic regression analyses to optimize discrimination of outcomes between patients treated with 10 mg/kg belimumab and patients receiving placebo over the first 52 weeks of follow-up. In addition, the performance of LuMOS was assessed using an independent validation data set from the BLISS-52 trial.
The LuMOS model incorporated the following response criteria: a ≥4-point reduction on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index, an increase in C4 levels, a decrease in anti-double-stranded DNA titers, and changes in the British Isles Lupus Assessment Group scores for organ system manifestations (no worsening in renal components, and improvements in mucocutaneous components). A decrease in the prednisone dose and increase in C3 levels had very minor impacts on the total LuMOS score. In all analyses of the BLISS-76 and BLISS-52 trial data sets, the mean LuMOS scores were significantly higher (P < 0.0001) in patients treated with 1 mg or 10 mg belimumab compared to placebo. In contrast to the performance of the SLE Responder Index 4 (SRI-4), the LuMOS revealed significant differences between the active treatment group (1 mg belimumab in the BLISS-76 cohort) and placebo group. The effect sizes were significantly much higher with the LuMOS than with the SRI-4.
The evidenced-based LuMOS outcome scoring system, developed with data from the BLISS-76 trial of belimumab in patients with SLE and validated with data from the BLISS-52 trial, exhibits a superior capacity to discriminate responders from nonresponders when compared to the SRI-4. Use of the LuMOS may improve the efficiency and power of analyses in future lupus trials.
新的系统性红斑狼疮（SLE）治疗试验受到缺乏有效结局指标的阻碍。为了解决这个问题，我们开发了一种新的狼疮多变量结局评分（LuMOS），并使用来自两项贝鲁单抗治疗 SLE 患者的随机对照试验的数据评估了其性能。
LuMOS 公式是通过分析两项关键试验（BLISS-52 研究和 BLISS-76 研究）的原始数据开发的，这两项试验是贝鲁单抗批准的基础。使用 BLISS-76 试验数据作为学习数据集，我们进行了多变量逻辑回归分析，以优化在随访的前 52 周内接受 10mg/kg 贝鲁单抗治疗的患者和接受安慰剂治疗的患者之间结局的区分能力。此外，还使用来自 BLISS-52 试验的独立验证数据集评估了 LuMOS 的性能。
LuMOS 模型纳入了以下反应标准：SLE 疾病活动指数的安全性雌激素评估版本（Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index）上≥4 分的降低、C4 水平的增加、抗双链 DNA 滴度的降低以及英国狼疮评估组评分的变化（肾脏成分无恶化，粘膜皮肤成分改善）。泼尼松剂量的减少和 C3 水平的增加对总 LuMOS 评分的影响很小。在对 BLISS-76 和 BLISS-52 试验数据集的所有分析中，与安慰剂相比，接受 1mg 或 10mg 贝鲁单抗治疗的患者的平均 LuMOS 评分显著更高（P < 0.0001）。与 SLE 应答者指数 4（SRI-4）的表现相反，LuMOS 显示了活性治疗组（BLISS-76 队列中的 1mg 贝鲁单抗）与安慰剂组之间的显著差异。LuMOS 的效应大小明显高于 SRI-4。
基于 BLISS-76 试验中贝鲁单抗治疗 SLE 患者的数据开发并使用 BLISS-52 试验的数据验证的基于证据的 LuMOS 结局评分系统，在区分应答者和无应答者方面表现出比 SRI-4 更高的能力。在未来的狼疮试验中使用 LuMOS 可能会提高分析的效率和能力。
