van den Hoogen F H, Boerbooms A M, Swaak A J, Rasker J J, van Lier H J, van de Putte L B
Department of Rheumatology, University Hospital, Nijmegen, The Netherlands.
Br J Rheumatol. 1996 Apr;35(4):364-72. doi: 10.1093/rheumatology/35.4.364.
In this study, methotrexate (MTX) was compared with placebo in the treatment of systemic sclerosis (scleroderma, SSc) in a 24 week randomized double-blind trial, followed by an observational trial of 24 weeks duration. Twenty-nine scleroderma patients were allocated to receive weekly injections of either 15 mg MTX or placebo. Patients who responded favourably after 24 weeks continued with the same regimen for a further 24 weeks; those who showed a poor response on placebo were allocated to further treatment with 15 mg MTX weekly, and those who responded poorly to treatment with 15 mg MTX had their doses increased to 25 mg. A favourable response was defined as an improvement of total skin score (TSS) by > or = 30%, of single breath diffusion capacity (DLCO) by > or = 15%, or of the score on a visual analogue scale of general well-being (VAS) by > or = 30%, provided that such improvements were not accompanied by persistent digital ulcerations or worsening of DLCO > or = 15%. Seventeen patients were allocated to MTX treatment and 12 to treatment with placebo. After 24 weeks, a significantly larger number of patients receiving MTX (n = 8, 53%) who completed the first 24 weeks of the study had responded favourably compared to patients receiving placebo (n = 1, 10%, P = 0.03). Comparison of separate variables between the two treatment groups by intention-to-treat analysis at week 24 showed improvement in the MTX group of TSS (P = 0.06) and creatinine clearance (P = 0.07). At week 48, 13 patients received MTX from the start of the study and nine during 24 weeks. From these 22 patients, 15(68%) responded favourably and compared with the start of the study they showed significant improvement of TSS (P = 0.04), VAS (P = 0.02), grip strength of the right hand (P = 0.02) and ESR (P = 0.01). Although the number of patients enrolled in this study is small, these results suggest that in a group of patients with active systemic sclerosis, low-dose MTX seems to be more effective than placebo according to pre-defined response criteria.
在本研究中，在一项为期24周的随机双盲试验中，将甲氨蝶呤（MTX）与安慰剂用于治疗系统性硬化症（硬皮病，SSc）进行比较，随后进行为期24周的观察性试验。29例硬皮病患者被分配接受每周一次15mg MTX或安慰剂注射。24周后反应良好的患者继续使用相同方案再治疗24周；安慰剂治疗反应不佳的患者被分配接受每周15mg MTX的进一步治疗，而15mg MTX治疗反应不佳的患者其剂量增加至25mg。若总皮肤评分（TSS）改善≥30%、单次呼吸弥散容量（DLCO）改善≥15%或总体健康视觉模拟量表（VAS）评分改善≥30%，且这些改善未伴有持续性指端溃疡或DLCO恶化≥15%，则定义为反应良好。17例患者被分配接受MTX治疗，12例接受安慰剂治疗。24周后，完成研究前24周的接受MTX治疗的患者（n = 8，53%）反应良好的人数显著多于接受安慰剂治疗的患者（n = 1，10%，P = 0.03）。在第24周通过意向性分析对两个治疗组的单独变量进行比较，结果显示MTX组的TSS（P = 0.06）和肌酐清除率（P = 0.07）有所改善。在第48周，13例患者从研究开始就接受MTX治疗，9例在24周期间接受治疗。在这22例患者中，15例（68%）反应良好，与研究开始时相比，他们的TSS（P = 0.04）、VAS（P = 0.02）、右手握力（P = 0.02）和红细胞沉降率（ESR）（P = 0.01）均有显著改善。尽管本研究纳入的患者数量较少，但这些结果表明，在一组活动性系统性硬化症患者中，根据预先定义的反应标准，低剂量MTX似乎比安慰剂更有效。
