Fleischmann Roy, Hayes Kyle, Ahn Sung-Woo, Wan George J, Panaccio Mary P, Karlsson Daniel, Furst Daniel E
Metroplex Clinical Research Center, University of Texas Southwestern Medical Center, 8144 Walnut Hill Lane, Dallas, TX, 75231, USA.
Mallinckrodt Pharmaceuticals, Hampton, NJ, USA.
Rheumatol Ther. 2022 Apr;9(2):435-446. doi: 10.1007/s40744-021-00412-x. Epub 2021 Dec 17.
Approximately 6% of patients with rheumatoid arthritis (RA) in the USA have refractory disease that is resistant to standard-of-care therapies. A recent phase IV clinical trial affirmed the safety and efficacy of repository corticotropin injection (RCI; Acthar® Gel) for refractory RA. This post hoc analysis of the clinical trial data assessed whether changes in clinical measures correlated with patient-reported outcome (PRO) improvements.
Data were assessed from the trial's open-label period when patients received RCI (80 U) twice weekly for 12 weeks. Clinical assessments included hemoglobin A1c, C-reactive protein, erythrocyte sedimentation rate (ESR), total joint count (TJC), swollen joint count (SJC), Disease Activity Score with 28 joint count and ESR (DAS28-ESR), and Clinical Disease Activity Index (CDAI). PROs included pain (Visual Analog Scale), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and activity impairment (Work Productivity and Activity Impairment [WPAI] questionnaire). Patients grouped by minimal clinically important difference (MCID) improvement vs no improvement in PROs were compared with clinical measures at week 12. Correlations were determined by multivariable linear regression analysis and standardized coefficient estimates.
RCI responders, defined as patients with DAS28-ESR < 3.2 at week 12, reported significantly greater PRO improvements for pain, disability, fatigue, activity impairment, current work impairment, and overall work impairment than nonresponders. Patients with MCID improvements in all PROs showed significantly greater decreases in mean values for TJC, DAS28-ESR, and CDAI, whereas those with pain, fatigue, and disability improvements had significantly greater SJC and ESR reductions. Multivariable linear regression analysis determined that improvement from baseline in all PROs correlated with significant decreases in TJC, DAS28-ESR, and CDAI. ESR reduction significantly correlated with improvements in pain and disability, but not fatigue or WPAI.
These results confirm that clinical responses to RCI were directly correlated with patient perception of improvement.
在美国，约6%的类风湿关节炎（RA）患者患有难治性疾病，对标准治疗方案耐药。最近一项IV期临床试验证实了储存促肾上腺皮质激素注射剂（RCI；Acthar® Gel）治疗难治性RA的安全性和有效性。这项对临床试验数据的事后分析评估了临床指标的变化是否与患者报告的结局（PRO）改善相关。
评估的数据来自试验的开放标签期，在此期间患者每周接受两次RCI（80 U），共12周。临床评估包括糖化血红蛋白、C反应蛋白、红细胞沉降率（ESR）、总关节计数（TJC）、肿胀关节计数（SJC）、基于28个关节计数和ESR的疾病活动评分（DAS28-ESR）以及临床疾病活动指数（CDAI）。PRO包括疼痛（视觉模拟量表）、疲劳（慢性病治疗功能评估-疲劳[FACIT-F]）、残疾（健康评估问卷-残疾指数[HAQ-DI]）和活动障碍（工作效率和活动障碍[WPAI]问卷）。将根据PRO中最小临床重要差异（MCID）改善与否分组的患者与第12周时的临床指标进行比较。通过多变量线性回归分析和标准化系数估计来确定相关性。
在第12周时定义为DAS28-ESR<3.2的患者为RCI应答者，与无应答者相比，他们在疼痛、残疾、疲劳、活动障碍、当前工作障碍和总体工作障碍方面的PRO改善显著更大。所有PRO均有MCID改善的患者，其TJC、DAS28-ESR和CDAI的平均值下降幅度显著更大，而在疼痛、疲劳和残疾方面有改善的患者，其SJC和ESR下降幅度显著更大。多变量线性回归分析确定，所有PRO相对于基线的改善与TJC、DAS28-ESR和CDAI的显著下降相关。ESR降低与疼痛和残疾的改善显著相关，但与疲劳或WPAI无关。
这些结果证实，对RCI的临床反应与患者对改善的感知直接相关。
