ARC Epidemiology Unit, Stopford Building, University of Manchester, Manchester M13 9PL, United Kingdom.
J Rheumatol. 2010 Jan;37(1):116-24. doi: 10.3899/jrheum.090668. Epub 2009 Dec 1.
Randomized clinical trials in early diffuse cutaneous systemic sclerosis (dcSSc) are challenging. We used an observational approach to estimate the relative effectiveness of different current treatment approaches, capturing entry and outcome data in a standardized way.
Patients with dcSSc within 3 years of the onset of skin thickening were included. Standardized entry and followup data were collected in relation to the first disease-modifying treatment at baseline and 4-6 weeks, then 3, 6, 12, 18, 24, 30, and 36 months. The 5 different protocols were (1) intravenous cyclophosphamide followed by mycophenolate mofetil (MMF); (2) antithymocyte globulin followed by MMF; (3) MMF alone; (4) no disease-modifying treatment; (5) other immunosuppressant treatment. The primary outcome measure was the modified Rodnan skin score (mRSS). Inverse probability of treatment weights were used to allow for differing patient characteristics between groups.
The study included 147 patients from 12 centers. Numbers of patients starting on Protocols 1 to 5 were 29, 25, 61, 19, and 13, respectively. mRSS decreased over time from 24 (IQ 19-32) at baseline to 15.5 (IQ 9-24.5) at 3 years. Although there were differences in the magnitude of the change for different protocols, there were no significant differences between protocols in the rate of change of mRSS over time (p = 0.43). When inverse probability weights were applied, the results remained nonsignificant (p = 0.41).
Using this observational approach, there were no obvious differences in outcome between groups after allowing as far as possible for baseline differences in treatment allocations.
早期弥漫性皮肤系统性硬化症（dcSSc）的随机临床试验具有挑战性。我们采用观察性方法来评估不同当前治疗方法的相对有效性，以标准化的方式捕获入组和结局数据。
纳入发病后 3 年内皮肤增厚的 dcSSc 患者。在基线和 4-6 周时，以及随后的 3、6、12、18、24、30 和 36 个月时，收集与首次疾病修正治疗相关的标准化入组和随访数据。5 种不同方案为：（1）静脉注射环磷酰胺后用霉酚酸酯（MMF）；（2）抗胸腺细胞球蛋白后用 MMF；（3）MMF 单独使用；（4）未使用疾病修正治疗；（5）其他免疫抑制剂治疗。主要结局指标为改良 Rodnan 皮肤评分（mRSS）。采用治疗概率逆加权来允许组间存在不同的患者特征。
本研究纳入了来自 12 个中心的 147 例患者。分别有 29、25、61、19 和 13 例患者开始接受方案 1 至 5 的治疗。mRSS 从基线时的 24（19-32）分逐渐下降，至 3 年时为 15.5（9-24.5）分。尽管不同方案的变化幅度有所不同，但 mRSS 随时间的变化率在方案之间没有显著差异（p=0.43）。应用逆概率权重后，结果仍无统计学意义（p=0.41）。
通过这种观察性方法，在尽可能考虑到治疗分配的基线差异后，各组之间的结局没有明显差异。
