Seymour Matthew W, Kelly Stephen, Beals Chan R, Malice Marie-Pierre, Bolognese James A, Dardzinski Bernard J, Cheng Amy S, Cummings Corinne E, Smugar Steven S, McClinton Catherine, Fox Amy, Dooley William M, Pitzalis Constantino, Taylor Peter C
Arthritis Res Ther. 2012 Sep 12;14(5):R198. doi: 10.1186/ar4034.
We aimed to investigate the sensitivity and reliability of two-dimensional ultrasonographic endpoints at the metacarpophalageal joints (MCPJs) and their potential to provide an early and objective indication of a therapeutic response to treatment intervention in rheumatoid arthritis (RA).
A randomized, double-blind, parallel-group, two-center, placebo-controlled trial investigated the effect on ultrasonographic measures of synovitis of repeat dose oral prednisone, 15 mg or 7.5 mg, each compared to placebo, in consecutive two-week studies; there were 18 subjects in a 1:1 ratio and 27 subjects in a 2:1 ratio, respectively. All subjects met the 1987 American College of Rheumatology criteria for the diagnosis of RA, were ≥18 years-old with RA disease duration ≥6 months, and had a Disease Activity Score 28 based on C-reactive protein (DAS28(CRP)) ≥3.2. Subjects underwent high-frequency (gray-scale) and power Doppler ultrasonography at Days 1 (baseline), 2, 8 and 15 in the dorsal transverse and longitudinal planes of all 10 MCPJs to obtain summated scores of quantitative and semi-quantitative measures of synovial thickness as well as vascularity. The primary endpoint was the summated score of power Doppler area measured quantitatively in all 10 MCPJs in the transverse plane at Day 15. Clinical efficacy was assessed at the same time points by DAS28(CRP).
All randomized subjects completed the trial. The comparison between daily 15 mg prednisone and placebo at Day 15 yielded a statistically significant treatment effect (effect size = 1.17, P = 0.013) in change from baseline in the primary endpoint, but borderline for prednisone 7.5 mg daily versus placebo (effect size = 0.61, P = 0.071). A significant treatment effect for DAS28(CRP) was only observed at Day 15 in the prednisone 15 mg group (effect size = 0.95, P = 0.032). However, significant treatment effects at all time points for a variety of ultrasound (US) endpoints were detected with both prednisone doses; the largest observed effect size = 2.33. Combining US endpoints with DAS28(CRP) improved the registration of significant treatment effects. The parallel scan inter-reader reliability of summated 10 MCPJ scores were good to excellent (ICC values >0.61) for the majority of US measures.
Ultrasonography of MCPJs is an early, reliable indicator of therapeutic response in RA with potential to reduce patient numbers and length of trials designed to give preliminary indications of efficacy.
Clinicaltrials.gov identifier: NCT00746512.
我们旨在研究掌指关节（MCPJ）二维超声检查终点的敏感性和可靠性，以及其为类风湿关节炎（RA）治疗干预的治疗反应提供早期客观指标的潜力。
一项随机、双盲、平行组、双中心、安慰剂对照试验，在连续两周的研究中，研究了重复剂量口服泼尼松15mg或7.5mg与安慰剂相比，对滑膜炎超声测量指标的影响；分别有18名受试者按1:1比例分组，27名受试者按2:1比例分组。所有受试者均符合1987年美国风湿病学会RA诊断标准，年龄≥18岁，RA病程≥6个月，且基于C反应蛋白的疾病活动评分28（DAS28(CRP)）≥3.2。受试者在第1天（基线）、第2天、第8天和第15天，对所有10个MCPJ的背侧横切面和纵切面进行高频（灰阶）和能量多普勒超声检查，以获得滑膜厚度及血管形成的定量和半定量测量的总和评分。主要终点是在第15天横切面上所有10个MCPJ定量测量的能量多普勒面积总和评分。在相同时间点通过DAS28(CRP)评估临床疗效。
所有随机分组的受试者均完成试验。在第15天，每日15mg泼尼松与安慰剂相比，主要终点从基线的变化产生了具有统计学意义的治疗效果（效应大小=1.17，P=0.013），但每日7.5mg泼尼松与安慰剂相比接近临界值（效应大小=0.61，P=0.071）。仅在第15天，泼尼松15mg组观察到DAS28(CRP)有显著治疗效果（效应大小=0.95，P=0.032）。然而，两种泼尼松剂量在所有时间点对各种超声（US）终点均检测到显著治疗效果；观察到的最大效应大小=2.33。将US终点与DAS28(CRP)相结合可改善显著治疗效果的记录。对于大多数US测量，10个MCPJ总和评分的平行扫描阅片者间可靠性良好至优秀（ICC值>0.61）。
MCPJ的超声检查是RA治疗反应的早期可靠指标，有可能减少旨在给出疗效初步指标的试验中的患者数量和试验时长。
Clinicaltrials.gov标识符：NCT00746512。
