Liu Kuan, Tomlinson George, Reed Ann M, Huber Adam M, Saarela Olli, Bout-Tabaku Sharon M, Curran Megan, Dvergsten Jeffrey A, Eberhard Barbara A, Jung Lawrence K, Kim Susan, Ringold Sarah, Rouster-Steven Kelly A, Tesher Melissa, Wahezi Dawn M, Feldman Brian M
K. Liu, MMath, B.M. Feldman, MD, MSc, FRCPC, The Hospital for Sick Children, Toronto, and Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
G. Tomlinson, PhD, Department of Medicine, University Health Network, Toronto, Ontario, Canada.
J Rheumatol. 2021 Jan 1;48(1):114-122. doi: 10.3899/jrheum.190494. Epub 2020 Apr 1.
To determine the feasibility of comparing the Childhood Arthritis and Rheumatology ResearchAlliance (CARRA) consensus treatment plans (CTP) in treating moderate new-onset juvenile dermatomyositis (JDM) using the CARRA registry, and to establish appropriate analytic methods to control for confounding by indication and missing data.
A pilot cohort of 39 patients with JDM from the CARRA registry was studied. Patients were assigned by the treating physician, considering patient/family preferences, to 1 of 3 CTP: methotrexate (MTX) and prednisone (MP); intravenous (IV) methylprednisolone, MTX, and prednisone (MMP); or IV methylprednisolone, MTX, prednisone, and IV immunoglobulin (MMPI). The primary outcome was the proportion of patients achieving moderate improvement at 6 months under each CTP. Statistical methods including multiple imputation and inverse probability of treatment weighting were used to handle missing data and confounding by indication.
Patients received MP (n = 13), MMP (n = 18) and MMPI (n = 8). Patients in all CTP had significant improvement in disease activity. Of the 36 patients who remained in our pilot study at 6 months, 16 (44%) of them successfully achieved moderate improvement at 6 months (6/13, 46% for MP; 7/15, 47% for MMP; 3/8, 38% for MMPI). After correcting for confounding, there were no statistically significant pairwise differences between the CTP ( = 0.328-0.88).
We gained valuable experience and insight from our pilot study that can be used to guide the design and analysis of comparative effectiveness studies using the CARRA registry CTP approach. Our analytical methods can be adopted for future comparative effectiveness studies and applied to other rare disease observational studies.
利用儿童关节炎与风湿病研究联盟（CARRA）注册库确定比较儿童关节炎与风湿病研究联盟共识治疗方案（CTP）治疗中度新发幼年皮肌炎（JDM）的可行性，并建立适当的分析方法以控制指示性偏倚和缺失数据。
对来自CARRA注册库的39例JDM患者的试点队列进行研究。治疗医师根据患者/家庭偏好，将患者分配至3种CTP方案之一：甲氨蝶呤（MTX）和泼尼松（MP）；静脉注射（IV）甲泼尼龙、MTX和泼尼松（MMP）；或IV甲泼尼龙、MTX、泼尼松和IV免疫球蛋白（MMPI）。主要结局是每种CTP方案下6个月时病情获得中度改善的患者比例。采用包括多重填补和治疗权重逆概率在内的统计方法处理缺失数据和指示性偏倚。
患者接受MP方案（n = 13）、MMP方案（n = 18）和MMPI方案（n = 8）。所有CTP方案组患者的疾病活动度均有显著改善。在6个月时仍留在我们试点研究中的36例患者中，16例（44%）在6个月时成功实现了中度改善（MP方案组6/13，46%；MMP方案组7/15，47%；MMPI方案组3/8，38%）。校正混杂因素后，各CTP方案之间无统计学显著的两两差异（P = 0.328 - 0.88）。
我们从试点研究中获得了宝贵的经验和见解，可用于指导采用CARRA注册库CTP方法的比较有效性研究的设计和分析。我们的分析方法可用于未来的比较有效性研究，并应用于其他罕见病观察性研究。
