Le Page Emmanuelle, Deburghgraeve Véronique, Lester Marie-Antoinette, Cardiet Isabelle, Leray Emmanuelle, Edan Gilles
Departement of Neurosciences, University Hospital Pontchaillou, 2 Rue Henri Guilloux, 35000, Rennes Cedex, France,
J Neurol. 2015;262(4):1024-34. doi: 10.1007/s00415-015-7653-3. Epub 2015 Feb 21.
Our study aimed to describe safety and neurological impact of alemtuzumab as last-line rescue therapy in aggressive multiple sclerosis (MS) patients, previously treated by Mitoxantrone (MITOX). Between June 2004 and October 2013, 13 patients received alemtuzumab at 20 mg/day and 3 at 12 mg/day for 5 days. EDSS, relapses, secondary progression were prospectively assessed 12 and 6 months before treatment, at baseline and every 3 months. Mean follow-up was 6.2 years [1-10]. Mean age at alemtuzumab start was 40 years [26-49] for 8 Secondary Progressive (SP) and 30 years [26-35] for 8 Relapsing-Remitting (RR) patients. MS duration was 13.7 (± 3) and 8.3 (± 4) years, respectively. During the 12 months before alemtuzumab, annual relapse rate was 0.75 and 3.14, respectively and the 16 patients accumulated 2-30 new gadolinium enhancing lesions. 4 patients (suboptimal responders) received alemtuzumab during MITOX and 12 patients 1-7.8 years after MITOX. Out of 8 SPMS, 2 were disease free up to last visit (4.7 and 8 years), 5 improved or stabilized but only transiently and 1 worsened. Out of 8 RRMS, 1 remained stable up to last visit (8.7 years) despite 1 relapse and active MRI at 18 months and 7 improved (1-4 point EDSS): 4 remained disease free up to last visit (12, 24, 38 months and 7 years), 2 were successfully retreated at 25 and 33 months and 1 worsened progressively 24 months after alemtuzumab. 2 patients developed Grave's disease and 1 hypothyroidism. Alemtuzumab controls aggressive RRMS despite previous use of MITOX.
我们的研究旨在描述阿仑单抗作为挽救疗法用于先前接受米托蒽醌（MITOX）治疗的侵袭性多发性硬化症（MS）患者的安全性和对神经系统的影响。2004年6月至2013年10月期间，13例患者接受了每日20毫克的阿仑单抗治疗，3例患者接受了每日12毫克的阿仑单抗治疗，持续5天。在治疗前12个月和6个月、基线时以及每3个月对扩展残疾状态量表（EDSS）、复发情况、继发进展进行前瞻性评估。平均随访时间为6.2年[1 - 10年]。开始使用阿仑单抗时，8例继发进展型（SP）患者的平均年龄为40岁[26 - 49岁]，8例复发缓解型（RR）患者的平均年龄为30岁[26 - 35岁]。MS病程分别为13.7（±3）年和8.3（±4）年。在使用阿仑单抗前的12个月内，年复发率分别为0.75和3.14，16例患者共出现2 - 30个新的钆增强病灶。4例患者（反应欠佳者）在使用MITOX期间接受了阿仑单抗治疗，12例患者在使用MITOX后1 - 7.8年接受了阿仑单抗治疗。在8例SPMS患者中，2例直至最后一次随访（4.7年和8年）无疾病进展，5例病情改善或稳定但仅为短暂性，1例病情恶化。在8例RRMS患者中，1例尽管有1次复发且在18个月时MRI显示有活动病灶，但直至最后一次随访（8.7年）病情仍保持稳定，7例病情改善（EDSS改善1 - 4分）：4例直至最后一次随访（12个月、24个月、38个月和7年）无疾病进展，2例在25个月和33个月时成功接受再次治疗，1例在使用阿仑单抗24个月后病情逐渐恶化。2例患者发生格雷夫斯病，1例发生甲状腺功能减退。尽管先前使用过MITOX，但阿仑单抗可控制侵袭性RRMS。
