Sipe J C, Romine J S, Koziol J A, McMillan R, Zyroff J, Beutler E
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037.
Lancet. 1994 Jul 2;344(8914):9-13. doi: 10.1016/s0140-6736(94)91046-4.
Chronic progressive multiple sclerosis (MS) is a severely disabling demyelinating disease in which autoimmune processes seem to have a major role. The nucleoside drug cladribine is a potent lympholytic agent with few side-effects. We have studied its efficacy and safety in a randomised double-blind trial. 51 patients (48 entered as matched pairs) received four monthly courses of 0.7 mg/kg cladribine or placebo (saline) given through a surgically implanted central line. Neurologists with no knowledge of which medication the patient was receiving examined the patients monthly and noted two rating scale scores (Kurtzke and Scripps). Cerebrospinal fluid and brain magnetic resonance imaging (MRI) examinations were done at 6 and 12 months. Average neurological scores, demyelinated volumes on MRI, and concentrations of oligoclonal bands in cerebrospinal fluid were stable or improved in the patients receiving cladrabine but continued to deteriorate in patients on placebo. Mean paired (placebo minus matched cladribine) differences at 12 months relative to baseline were 1.0 (SE 0.4) for the Kurtzke scores, -13.9 (2.3) for the Scripps scores, 4.57 (1.17) mL for demyelinated volumes, and 7.3 (3.3) arbitrary units for concentrations of oligoclonal bands. Cladribine was generally well tolerated and clinically significant toxicity occurred in only 1 patient, in whom severe marrow suppression developed with complete recovery after several months. 1 patient died of newly acquired hepatitis B, an event unlikely to be related to cladribine. We conclude that the immunosuppressive drug cladribine influences favourably the course of chronic progressive MS.
慢性进行性多发性硬化症（MS）是一种严重致残的脱髓鞘疾病，自身免疫过程似乎在其中起主要作用。核苷类药物克拉屈滨是一种有效的淋巴细胞溶解剂，副作用较少。我们在一项随机双盲试验中研究了其疗效和安全性。51名患者（48名以配对形式入组）通过手术植入的中心静脉导管接受了4个每月疗程的0.7mg/kg克拉屈滨或安慰剂（生理盐水）治疗。对患者用药情况不知情的神经科医生每月对患者进行检查，并记录两个评分量表得分（库尔特克和斯克里普斯）。在6个月和12个月时进行脑脊液和脑磁共振成像（MRI）检查。接受克拉屈滨治疗的患者的平均神经学评分、MRI上的脱髓鞘体积以及脑脊液中寡克隆带的浓度保持稳定或有所改善，而接受安慰剂治疗的患者则持续恶化。相对于基线，12个月时的平均配对（安慰剂减去配对的克拉屈滨）差异在库尔特克评分中为1.0（标准误0.4），在斯克里普斯评分中为-13.9（2.3），脱髓鞘体积为4.57（1.17）mL，寡克隆带浓度为7.3（3.3）个任意单位。克拉屈滨总体耐受性良好，仅1例患者出现具有临床意义的毒性反应，该患者出现严重骨髓抑制，数月后完全恢复。1例患者死于新感染的乙型肝炎，这一事件不太可能与克拉屈滨有关。我们得出结论，免疫抑制药物克拉屈滨对慢性进行性MS的病程有有利影响。
