Reggio Ester, Nicoletti Alessandra, Fiorilla Teresa, Politi Guido, Reggio Arturo, Patti Francesco
Centre of Multiple Sclerosis and Degenerative Disease of the Nervous System, University of Catania, Via Conti 6, Italy.
J Neurol. 2005 Oct;252(10):1255-61. doi: 10.1007/s00415-005-0857-1. Epub 2005 Jun 6.
The aim of the present study was to evaluate the efficacy of the combination of cyclophosphamide (CTX) and interferon beta (IFN beta) in a group of relapsing remitting (RR) multiple sclerosis (MS) patients who experienced treatment failure during IFN beta therapy. It is the general experience that immunomodulatory agents (IMA) are only partially effective in RR patients. Recent data on the efficacy of immunosuppressive therapies for these patients are encouraging. The anti-inflammatory and immunosuppressive effects of CTX have been utilized to treat selected cases of multiple sclerosis with a progressive and worsening course as rescue therapy. Thirty RR MS patients with clinically defined MS who experienced treatment failure during IFN beta therapy (2 or more relapses per year or 1.5 EDSS point worsening in one year) were enrolled in the study and treated with CTX iv pulse therapy added to IFN beta and followed up for 24 months. As primary endpoints we evaluated the yearly relapse rate. We also evaluated the percentage of patients free of relapses and of EDSS variations. We analysed the results at one year before entry (T0: IFN beta alone), 12 (T1) and 24 (T2) months after entry. Brain MRI was performed at T0, at T1 and T2. The 30 RR patients who had experienced a high number of relapses (rr =1.4) at T0 showed a significant improvement in yearly relapse rate (rr = 0.4) at T1 and a further improvement (rr = 0.17) at T2 (p < 0.001). The percentage of patients free of relapse was 70% at T2 (p < 0.0001). EDSS score changed from 2.6+/-1.23 at T0 to 2.2 +/- 1.5 at T2, showing only a trend of improvement. No significant variation of MRI lesion load and no severe adverse events were recorded during the study. These data showed that the combination of CTX plus IFN beta halted the progression of disease in active and deteriorating MS patients suggesting the necessity of RCTs to test the efficacy of this combination therapy in active RRMS patients or in patients who experienced treatment failure in response to disease modifying drugs (DMDs).
本研究的目的是评估环磷酰胺（CTX）与β-干扰素（IFNβ）联合用药对一组复发缓解型（RR）多发性硬化症（MS）患者的疗效，这些患者在IFNβ治疗期间出现了治疗失败。一般经验表明，免疫调节药物（IMA）对RR患者仅部分有效。近期关于这些患者免疫抑制治疗疗效的数据令人鼓舞。CTX的抗炎和免疫抑制作用已被用于治疗部分多发性硬化症进展性恶化病例，作为挽救疗法。30例临床确诊为MS且在IFNβ治疗期间出现治疗失败（每年复发2次或以上或一年内扩展残疾状态量表（EDSS）评分恶化1.5分）的RR MS患者被纳入研究，接受在IFNβ基础上加用CTX静脉脉冲治疗，并随访24个月。作为主要终点，我们评估了年复发率。我们还评估了无复发患者的百分比以及EDSS变化情况。我们分析了入组前一年（T0：仅使用IFNβ）、入组后12个月（T1）和24个月（T2）的结果。在T0、T1和T2时进行脑部磁共振成像（MRI）检查。30例在T0时复发次数较多（rr = 1.4）的RR患者在T1时年复发率显著改善（rr = 0.4），在T2时进一步改善（rr = 0.17）（p < 0.001）。在T2时无复发患者的百分比为70%（p < 0.0001）。EDSS评分从T0时的2.6±1.23变为T2时的2.2±1.5，仅显示出改善趋势。在研究期间未记录到MRI病灶负荷的显著变化，也未出现严重不良事件。这些数据表明，CTX加IFNβ的联合用药可阻止活动性和病情恶化的MS患者疾病进展，提示有必要进行随机对照试验（RCT）来测试这种联合治疗对活动性RRMS患者或对疾病修饰药物（DMDs）治疗失败患者的疗效。
