Merkel Peter A, Herlyn Karen, Martin Richard W, Anderson Jennifer J, Mayes Maureen D, Bell Patrice, Korn Joseph H, Simms Robert W, Csuka Mary Ellen, Medsger Thomas A, Rothfield Naomi F, Ellman Michael H, Collier David H, Weinstein Arthur, Furst Daniel E, Jiménez Sergio A, White Barbara, Seibold James R, Wigley Fredrick M
Harvard Medical School, Boston, Massachusetts, USA.
Arthritis Rheum. 2002 Sep;46(9):2410-20. doi: 10.1002/art.10486.
To document disease activity and functional status in patients with scleroderma (systemic sclerosis [SSc]) and Raynaud's phenomenon (RP) and to determine the sensitivity to change, reliability, ease of use, and validity of various outcome measures in these patients.
Patients with SSc and moderate-to-severe RP participating in a multicenter RP treatment trial completed daily diaries documenting the frequency and duration of RP attacks and recorded a daily Raynaud's Condition Score (RCS). Mean scores for the 2-week periods prior to baseline (week 0), end of trial (week 6), and posttrial followup (week 12) were calculated. At weeks 0, 6, and 12, physicians completed 3 global assessment scales and performed clinical assessments of digital ulcers and infarcts; patients completed the Health Assessment Questionnaire (HAQ), the Arthritis Impact Measurement Scales 2 (AIMS2) mood and tension subscales, 5 specific SSc/RP-related visual analog scales (VAS), and 3 other VAS global assessments. We used these measures to document baseline disease activity and to assess their construct validity, sensitivity to change, and reliability in trial data.
Two hundred eighty-one patients (248 women, 33 men; mean age 50.4 years [range 18-82 years]) from 14 centers participated. Forty-eight percent had limited cutaneous SSc; 52% had diffuse cutaneous SSc. Fifty-nine patients (21%) had digital ulcers at baseline. Patients had 3.89 +/- 2.33 (mean +/- SD) daily RP attacks (range 0.8-14.6), with a duration of 82.1 +/- 91.6 minutes/attack. RCS for RP activity (possible range 0-10) was 4.30 +/- 1.92. HAQ scores (0-3 scale) indicated substantial disability at baseline (total disability 0.86, pain 1.19), especially among the subscales pertaining to hand function (grip, eating, dressing). AIMS2 mood and tension scores were fairly high, as were many of the VAS scores. Patients with digital ulcers had worse RCS, pain, HAQ disability (overall, grip, eating, and dressing), physician's global assessment, and tension, but no significant difference in the frequency of RP, duration of RP, patient's global assessment, or mood, compared with patients without digital ulcers. VAS scores for digital ulcers as rated by the patients were not consistent with the physician's ratings. Factor analysis of the 18 measures showed strong associations among variables in 4 distinct domains: disease activity, RP measures, digital ulcer measures, and mood/tension. Reliability of the RCS, HAQ pain and disability scales, and AIMS2 mood and tension subscales was high. The RP measures demonstrated good sensitivity to change (effect sizes 0.33-0.76).
Our findings demonstrate that the significant activity, disability, pain, and psychological impact of RP and digital ulcers in SSc can be measured by a small set of valid and reliable outcome measures. These outcome measures provide information beyond the quantitative metrics of RP attacks. We propose a core set of measures for use in clinical trials of RP in SSc patients that includes the RCS, patient and physician VAS ratings of RP activity, a digital ulcer/infarct measure, measures of disability and pain (HAQ), and measures of psychological function (AIMS2).
记录硬皮病（系统性硬化症[SSc]）和雷诺现象（RP）患者的疾病活动度和功能状态，并确定这些患者中各种结局指标的变化敏感性、可靠性、易用性和有效性。
参与一项多中心RP治疗试验的SSc和中重度RP患者完成每日日记，记录RP发作的频率和持续时间，并记录每日雷诺病情评分（RCS）。计算基线（第0周）、试验结束时（第6周）和试验后随访（第12周）前2周的平均评分。在第0、6和12周，医生完成3项整体评估量表，并对指端溃疡和梗死进行临床评估；患者完成健康评估问卷（HAQ）、关节炎影响测量量表2（AIMS2）情绪和紧张分量表、5项特定的SSc/RP相关视觉模拟量表（VAS）以及3项其他VAS整体评估。我们使用这些指标记录基线疾病活动度，并评估其结构效度、变化敏感性和试验数据中的可靠性。
来自14个中心的281例患者（248例女性，33例男性；平均年龄50.4岁[范围18 - 82岁]）参与研究。48%为局限性皮肤型SSc；52%为弥漫性皮肤型SSc。59例患者（21%）在基线时有指端溃疡。患者每日RP发作3.89±2.33次（平均±标准差，范围0.8 - 14.6次），每次发作持续82.1±91.6分钟。RP活动的RCS（可能范围0 - 10）为4.30±1.92。HAQ评分（0 - 3分制）显示基线时存在严重残疾（总残疾0.86，疼痛1.19），尤其是在与手部功能相关的分量表中（握力、进食、穿衣）。AIMS2情绪和紧张评分相当高，许多VAS评分也是如此。与无指端溃疡的患者相比，有指端溃疡的患者RCS、疼痛、HAQ残疾（总体、握力、进食和穿衣）、医生整体评估和紧张程度更差，但在RP频率、RP持续时间、患者整体评估或情绪方面无显著差异。患者对指端溃疡的VAS评分与医生的评分不一致。对这18项指标的因子分析显示，4个不同领域的变量之间存在强关联：疾病活动度、RP指标、指端溃疡指标以及情绪/紧张。RCS、HAQ疼痛和残疾量表以及AIMS2情绪和紧张分量表的可靠性较高。RP指标显示出良好的变化敏感性（效应大小0.33 - 0.76）。
我们的研究结果表明，一小套有效且可靠的结局指标可以衡量SSc中RP和指端溃疡的显著活动度、残疾程度、疼痛和心理影响。这些结局指标提供了超出RP发作定量指标的信息。我们提出了一组核心指标，用于SSc患者RP临床试验，包括RCS、患者和医生对RP活动的VAS评分、指端溃疡/梗死指标、残疾和疼痛指标（HAQ）以及心理功能指标（AIMS2）。
