Centre for Musculoskeletal Research, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
NIHR Manchester Musculoskeletal Biomedical Research Centre, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Ann Rheum Dis. 2018 Apr;77(4):563-570. doi: 10.1136/annrheumdis-2017-211912. Epub 2018 Jan 6.
Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs).
The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV).
66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%.
Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years.
NCT02339441.
我们旨在利用欧洲硬皮病观察性研究提供的机会：(1) 确定并描述那些早期弥漫性皮肤系统性硬皮病（dcSSc）且皮肤厚度逐渐增加的患者；(2) 为 12 个月内的进展情况建立预测模型，以便为未来的随机对照试验（RCT）提供信息。
326 例患者每 3 个月记录一次改良 Rodnan 皮肤评分（mRSS）。“进展者”定义为 mRSS 评分在 12 个月内增加 5 个单位和 25%（±3 个月）。拟合逻辑模型以预测进展情况，并基于曲线下面积（AUC）、准确性和阳性预测值（PPV）比较 ROC 曲线。
66 例患者（22.5%）进展，227 例患者（77.5%）未进展（33 例由于数据不足无法评估其状态）。进展者的疾病持续时间较短（中位数 8.1 与 12.6 个月，P=0.001），mRSS 较低（中位数 19 与 21 单位，P=0.030）。抗 RNA 聚合酶 III（Pol3+）亚组（n=50）的皮肤评分最高，且最早达到峰值。第一个预测模型（包括 mRSS、皮肤增厚持续时间及其相互作用）的准确性为 60.9%，AUC 为 0.666，PPV 为 33.8%。通过增加 Pol3 阳性的变量，模型的准确性达到 71%，AUC 为 0.711，PPV 为 41%。
得出了两种用于进行性皮肤增厚的预测模型，既可以用于临床实践，也可以用于 RCT 中的队列富集。这些模型将为未来几年计划开展的许多 dcSSc 临床试验提供信息。
NCT02339441。
