De Mercanti Stefania Federica, Signori Alessio, Cordioli Cinzia, Signoriello Elisabetta, Lus Giacomo, Bonavita Simona, Abbadessa Gianmarco, Lavorgna Luigi, Maniscalco Giorgia Teresa, Curti Erica, Lorefice Lorena, Cocco Eleonora, Nociti Viviana, Mirabella Massimiliano, Baroncini Damiano, Mataluni Giorgia, Landi Doriana, Petruzzo Martina, Lanzillo Roberta, Gandoglia Ilaria, Laroni Alice, Frangiamore Rita, Sartori Arianna, Cavalla Paola, Costantini Gianfranco, Capra Ruggero, Sormani Maria Pia, Clerico Marinella
Clinical and Biological Sciences Department, Neurology Unit, University of Torino, San Luigi Gonzaga Hospital, Orbassano, Torino, Italy.
Department of Health Sciences, Section of Biostatistics, University of Genova, Italy.
J Neurol Sci. 2021 May 15;424:117385. doi: 10.1016/j.jns.2021.117385. Epub 2021 Mar 6.
To minimize the risk of Progressive Multifocal Leukoencephalopathy and rebound in JCV-positive multiple sclerosis (MS) patients after 24 natalizumab doses, it has been proposed to extend the administrations interval. The objective is to evaluate the EID efficacy on MRI activity compared with the standard interval dosing (SID).
Observational, multicentre, retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Three hundred and sixteen patients were enrolled. The median dose interval (MDI) following the 24th infusion was 5 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Patients were grouped into 2 categories according to the mean number of weeks between doses: <5 weeks, SID; ≥5 weeks, EID.
One hundred and eighty-seven patients were in the SID group (MDI = 4.5 weeks) and 129 in the EID group (MDI 6.1 weeks). The risk to develop active lesions on MRI is similar in SID and EID groups during the 6 and 12 months after the 24th natalizumab infusion, respectively 4.27% (95% CI:0.84-7.70) vs 4.71% (95% CI:0.16-9.25%) [p = 0.89] and 8.50% (95% CI:4.05-12.95) vs 6.55% (95% CI:2.11-11.00%) [p = 0.56]. The EID regimen does not appear to increase the occurrence of MRI activity during follow-up.
There is no evidence of the reduced efficacy of natalizumab in an EID setting regarding the MRI activity. This observation supports the need for a bigger randomized study to assess the need to change the standard of the natalizumab dosing schedule, to better manage JCV-positive patients.
为了将进行性多灶性白质脑病的风险以及那他珠单抗治疗24剂后的JC病毒（JCV）阳性多发性硬化症（MS）患者的病情反弹风险降至最低，有人建议延长给药间隔。目的是评估延长间隔给药（EID）与标准间隔给药（SID）相比对MRI活性的疗效。
观察性、多中心、回顾性队列研究，从第24次输注那他珠单抗开始至失访或基线后2年。共纳入316例患者。第24次输注后的中位剂量间隔（MDI）为5周，呈双峰分布（峰值在4周和6周）。根据剂量之间的平均周数将患者分为两类：<5周，SID；≥5周，EID。
187例患者在SID组（MDI = 4.5周），129例在EID组（MDI 6.1周）。在第24次输注那他珠单抗后的6个月和12个月内，SID组和EID组MRI上出现活动性病变的风险相似，分别为4.27%（95%CI：0.84 - 7.70）对4.71%（95%CI：0.16 - 9.25%）[p = 0.89]和8.50%（95%CI：4.05 - 12.95）对6.55%（95%CI：2.11 - 11.00%）[p = 0.56]。EID方案在随访期间似乎不会增加MRI活性的发生。
没有证据表明在EID情况下那他珠单抗在MRI活性方面疗效降低。这一观察结果支持需要进行更大规模的随机研究，以评估是否需要改变那他珠单抗给药方案的标准，从而更好地管理JCV阳性患者。
