Dalton Catherine M, Miszkiel Katherine A, Barker Gareth J, MacManus David G, Pepple Tracy I, Panzara Michael, Yang Minhua, Hulme Allison, O'Connor Paul, Miller David H
Institute of Neurology, London, UK.
J Neurol. 2004 Apr;251(4):407-13. doi: 10.1007/s00415-004-0332-4.
Natalizumab, a humanized monoclonal anti-adhesion molecule antibody, reduces the frequency of new gadolinium (Gd) enhancing lesions and relapses in multiple sclerosis (MS). Its effect on evolution of new Gd enhancing lesions to T1 hypointense lesions is unknown.
213 patients were randomized to receive 3 mg/kg or 6 mg/kg natalizumab or placebo monthly for 6 months and then followed for a further 6 months. A subset of patients who had one or more new gadolinium enhancing lesions from Month 0 to Month 6 and available electronic data were analysed. Each new Gd enhancing lesion that developed during treatment (months 1-6) was investigated for conversion to a new T1 hypointense lesion at month 12. Lesions were classified as large or small if their cross-sectional area was greater or less than 20 mm2. Because of the similarity of both doses of natalizumab on the frequency of new Gd enhancing lesions, the two natalizumab arms were combined in all analyses.
Compared with the placebo group, the natalizumab group exhibited significant decreases in: (i) the proportion of patients with new Gd enhancing lesions that evolved to T1-hypointense lesions (10/38 [26 %] versus 27/40 [68 %]; p<0.01); (ii) the proportion of patients who developed large T1 hypointense lesions (2/38 [5 %] versus 16/40 [40 %]; p<0.01); (iii) the proportion of new Gd enhancing lesions that became T1 hypointense (11/75 [15 %] versus 118/466 [25 %]; p=0.045); (iv) the mean proportion per patient of new Gd enhancing lesions that converted to T1-hypointense lesions (0.15 versus 0.28; p=0.005), and (v) the odds ratio (OR) of converting from Gd enhancing to T1-hypointense lesions (OR=0.48; 95% CI=0.24, 0.94, p=0.031).
Natalizumab significantly suppresses the evolution of new Gd enhancing to T1-hypointense lesions. This may reflect several mechanisms including reduced cell migration across the blood brain barrier, reduced T cell activation within lesions, an inhibitory effect on subsequent axonal damage within the new central nervous system lesion, and a reduced likelihood of recurrent lesion inflammation.
那他珠单抗是一种人源化单克隆抗黏附分子抗体，可降低多发性硬化症（MS）中新的钆（Gd）增强病灶的出现频率和复发率。其对新的Gd增强病灶演变为T1低信号病灶的影响尚不清楚。
213例患者被随机分为三组，分别每月接受3mg/kg或6mg/kg那他珠单抗或安慰剂治疗，为期6个月，然后再随访6个月。对0至6个月期间有一个或多个新的Gd增强病灶且有可用电子数据的患者亚组进行分析。研究治疗期间（第1至6个月）出现的每个新的Gd增强病灶在第12个月时是否转变为新的T1低信号病灶。如果病灶的横截面积大于或小于20mm²，则将其分类为大或小。由于两种剂量的那他珠单抗对新的Gd增强病灶频率的影响相似，因此在所有分析中将两个那他珠单抗组合并。
与安慰剂组相比，那他珠单抗组在以下方面有显著降低：（i）新的Gd增强病灶演变为T1低信号病灶的患者比例（10/38 [26%] 对27/40 [68%]；p<0.01）；（ii）出现大的T1低信号病灶的患者比例（2/38 [5%] 对16/40 [40%]；p<0.01）；（iii）新的Gd增强病灶转变为T1低信号的比例（11/75 [15%] 对118/466 [25%]；p=0.045）；（iv）每位患者新的Gd增强病灶转变为T1低信号病灶的平均比例（0.15对0.28；p=0.005），以及（v）从Gd增强病灶转变为T1低信号病灶的比值比（OR）（OR=0.48；95%CI=0.24，0.94，p=0.031）。
那他珠单抗显著抑制新的Gd增强病灶向T1低信号病灶的演变。这可能反映了多种机制，包括减少细胞穿过血脑屏障的迁移、减少病灶内T细胞的激活、对新的中枢神经系统病灶内后续轴突损伤的抑制作用以及复发性病灶炎症可能性的降低。
