Romme Christensen Jeppe, Ratzer Rikke, Börnsen Lars, Lyksborg Mark, Garde Ellen, Dyrby Tim B, Siebner Hartwig R, Sorensen Per S, Sellebjerg Finn
From the Danish Multiple Sclerosis Center (J.R.C., R.R., L.B., P.S.S., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen; Danish Research Center for Magnetic Resonance (M.L., E.G., T.B.D., H.R.S.), Copenhagen University Hospital Hvidovre, Denmark.
Neurology. 2014 Apr 29;82(17):1499-507. doi: 10.1212/WNL.0000000000000361. Epub 2014 Mar 28.
Natalizumab inhibits the migration of systemic immune cells to the CNS and may be beneficial in progressive multiple sclerosis (MS). The objective of the study was to examine the effects of natalizumab in progressive MS.
In an open-label phase 2A study, 24 patients with progressive MS were included to receive natalizumab treatment for 60 weeks. Response to natalizumab was assessed in CSF and MRI studies. The primary endpoint was change in CSF osteopontin, a biomarker of intrathecal inflammation, from baseline to week 60.
Seventeen patients completed the study. No new safety issues were encountered. CSF osteopontin decreased by 65 ng/mL (95% confidence interval 34-96 ng/mL; p = 0.0004) from baseline to week 60 in conjunction with decreases in other CSF biomarkers of inflammation, axonal damage, and demyelination. Magnetization transfer ratio increased in both cortical gray and normal-appearing white matter and correlated with decreases in CSF neurofilament light chain.
Natalizumab treatment of progressive MS reduces intrathecal inflammation and tissue damage, supporting a beneficial effect of natalizumab treatment in progressive MS and suggesting that systemic inflammation contributes to the pathogenesis. Moreover, the study establishes the feasibility of using CSF biomarkers in proof-of-concept trials, allowing a low number of participants and short study duration.
This study provides Class IV evidence that in patients with progressive MS, natalizumab reduces biomarkers of intrathecal inflammation.
那他珠单抗可抑制全身免疫细胞向中枢神经系统的迁移，可能对进展型多发性硬化症（MS）有益。本研究的目的是检验那他珠单抗对进展型MS的疗效。
在一项开放标签的2A期研究中，纳入24例进展型MS患者接受那他珠单抗治疗60周。通过脑脊液（CSF）和磁共振成像（MRI）研究评估对那他珠单抗的反应。主要终点是CSF骨桥蛋白（一种鞘内炎症的生物标志物）从基线到第60周的变化。
17例患者完成了研究。未遇到新的安全问题。从基线到第60周，CSF骨桥蛋白下降了65 ng/mL（95%置信区间34 - 96 ng/mL；p = 0.0004），同时其他CSF炎症、轴突损伤和脱髓鞘生物标志物也有所下降。皮质灰质和外观正常的白质的磁化传递率均增加，且与CSF神经丝轻链的下降相关。
那他珠单抗治疗进展型MS可减轻鞘内炎症和组织损伤，支持那他珠单抗治疗进展型MS具有有益作用，并提示全身炎症参与发病机制。此外，该研究确立了在概念验证试验中使用CSF生物标志物的可行性，允许参与者数量少且研究持续时间短。
本研究提供了IV类证据，表明在进展型MS患者中，那他珠单抗可降低鞘内炎症的生物标志物。
