Clinical and Biological Sciences Department, Neurology Unit, University of Torino, San Luigi Gonzaga Hospital, Regione Gonzole, 10, Orbassano, 10043, Turin, Italy.
Department of Health Sciences, Section of Biostatistics, University of Genova, Genoa, Italy.
Neurotherapeutics. 2020 Jan;17(1):200-207. doi: 10.1007/s13311-019-00776-7.
Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML). The objective is to evaluate the noninferiority of the efficacy of an extended interval dosing (EID) compared with the standard interval dosing (SID) of natalizumab. It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Three hundred and sixty patients were enrolled. Median dose interval (MDI) following 24th infusion was 4.7 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Two hundred and sixteen patients were in the SID group (MDI = 4.3 weeks) and 144 in the EID group (MDI 6.2 weeks). Annualized relapse rate was 0.060 (95% CI = 0.033-0.087) in the SID group and 0.039 (95% CI = 0.017-0.063) in the EID group. The non-inferiority of EID versus SID was satisfied. In conclusion, there is no evidence of a reduced efficacy of natalizumab in an EID setting. This observation confirms previous results and together with the emerging evidence of a reduced risk of PML associated to an EID, supports the need of a randomized study to assess the need to change the standard of the natalizumab dosing schedule.
延长第 24 次给药后的那他珠单抗间隔时间可降低进行性多灶性白质脑病（PML）的风险。目的是评估延长间隔给药（EID）与那他珠单抗标准间隔给药（SID）的疗效非劣效性。这是一项观察性、多中心（14 家意大利中心）、回顾性队列研究，从第 24 次那他珠单抗输注开始，直至随访丢失或基线后 2 年。根据剂量之间的平均周数，患者分为 2 组：<5 周，SID；≥5 周，EID。共纳入 360 例患者。第 24 次输注后中位剂量间隔（MDI）为 4.7 周，呈双峰分布（模式为 4 周和 6 周）。216 例患者在 SID 组（MDI=4.3 周），144 例在 EID 组（MDI 6.2 周）。SID 组的年复发率为 0.060（95%CI=0.033-0.087），EID 组为 0.039（95%CI=0.017-0.063）。EID 与 SID 的非劣效性得到满足。总之，在 EID 环境下，那他珠单抗的疗效没有降低的证据。这一观察结果证实了先前的结果，并且与 EID 相关的 PML 风险降低的新证据一起，支持需要进行一项随机研究来评估是否需要改变那他珠单抗给药方案的标准。
