Pandya Rachita, Dan Joshua, Kleitsch Julianne, White Barbara, Werth Victoria P
Corporal Micheal J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Corbus Pharmaceuticals, Norwood, Massachusetts, USA.
J Invest Dermatol. 2023 Dec;143(12):2378-2385.e7. doi: 10.1016/j.jid.2023.05.025. Epub 2023 Jun 16.
In the past decade, there have been six industry-sponsored phase 3 trials in adult patients with dermatomyositis (DM), primarily focusing on improving muscle weakness. However, skin disease is a cardinal manifestation of DM. This study evaluated the sensitivity of Cutaneous Dermatomyositis Disease Area and Severity Index Activity score, Cutaneous Dermatomyositis Activity Investigator Global Assessment, Total Improvement Score, and other outcome measures used in DM clinical trials to detect improvement in DM skin disease activity. Data analyzed from the lenabasum phase 3 trial in DM showed that improvement in Cutaneous Dermatomyositis Disease Area and Severity Index Activity score increased proportionately with the degree of patient- or physician-reported improvement in skin disease, consistently measuring improvement when clinically meaningful improvement was reported at weeks 16-52. In contrast, Cutaneous Dermatomyositis Activity Investigator Global Assessment measured little change from baseline with reported no improvement in skin disease but also a similar change from baseline with slight improvement. No Skindex-29+3 subscale performed well at reflecting increasing degrees of improvement in skin disease. Extramuscular Global Assessment and Total Improvement Score generally showed increasing levels of improvement as the degree of patient- and physician-reported improvement in skin disease increased, but these are composite measures and are not specific to improvement in DM skin disease. To measure clinically meaningful improvement in skin disease in a DM trial, Cutaneous Dermatomyositis Disease Area and Severity Index Activity score is the more sensitive outcome measure across time points.
在过去十年中，针对成年皮肌炎（DM）患者开展了六项由行业赞助的3期试验，主要聚焦于改善肌肉无力。然而，皮肤病变是DM的主要表现。本研究评估了皮肌炎皮肤病灶面积和严重程度指数活动评分、皮肌炎活动研究者整体评估、总体改善评分以及DM临床试验中用于检测DM皮肤疾病活动改善情况的其他结局指标的敏感性。对DM的lenabasum 3期试验数据分析显示，皮肌炎皮肤病灶面积和严重程度指数活动评分的改善与患者或医生报告的皮肤疾病改善程度成比例增加，在第16 - 52周报告有临床意义的改善时，始终能检测到改善情况。相比之下，皮肌炎活动研究者整体评估显示，在报告皮肤疾病无改善时，与基线相比变化不大，但在报告有轻微改善时，与基线的变化情况类似。没有Skindex - 29 + 3子量表能很好地反映皮肤疾病改善程度的增加。肌肉外整体评估和总体改善评分通常随着患者和医生报告的皮肤疾病改善程度增加而显示出改善水平的提高，但这些是综合指标，并非特定于DM皮肤疾病的改善情况。在DM试验中，为了衡量皮肤疾病有临床意义的改善，皮肌炎皮肤病灶面积和严重程度指数活动评分是跨时间点更敏感的结局指标。
