Background and Objectives Neuromyelitis optica spectrum disorder(NMOSD) is a rare debilitating autoimmune disease of the CNS.Three monoclonal antibodies were recently approved as maintenance therapies for aquaporin-4 immunoglobulin G(AQP4-IgG)–seropositive NMOSD (eculizumab,inebilizumab,and satralizumab),prompting the need to consider best practice therapeutic decisionmaking for this indication.Our objective was to develop validated statements for the management of AQP4-IgG–seropositive NMOSD,through an evidence-based Delphi consensus process,with a focus on recommendations for eculizumab,inebilizumab,and satralizumab.

Methods We recruited an international panel of clinical experts in NMOSD and asked them to complete a questionnaire on NMOSD management.Panel members received a summary of evidence identified through a targeted literature review and provided free-text responses to the questionnaire based on both the data provided and their clinical experience.Responses were used to generate draft statements on NMOSD-related themes.Statements were voted on over a maximum of 3 rounds；participation in at least 1 of the first 2 rounds was mandatory.Panel members anonymously provided their level of agreement (6-point Likert scale) on each statement. Statements that failed to reach a predefined consensus threshold (≥67%) were revised based on feedback and then voted on in the next round.Final statements were those that met the consensus threshold (≥67%).

Results The Delphi panel comprised 24 experts,who completed the Delphi process in November 2021 after 2 voting rounds. In round 1,23/25 statements reached consensus and were accepted as final. The 2 statements that failed to reach consensus were revised.In round 2,both revised statements reached consensus.Twenty-five statements were agreed in total:11 on initiation of or switching between eculizumab, inebilizumab,and satralizumab；3 on monotherapy/combination therapy；7 on safety and patient population considerations；3 on biomarkers/patient-reported outcomes; and 1 on research gaps.

Discussion An established consensus method was used to develop statements relevant to the management of AQP4-IgG–seropositive NMOSD.These international statements will be valuable for informing individualized therapeutic decision-making and could form the basis for standardized practice guidelines.

背景和目的 视神经脊髓炎谱系障碍(NMOSD)是一种罕见的使人衰弱的CNS自身免疫性疾病。最近批准了3种单克隆抗体作为水通道蛋白-4免疫球蛋白G(AQP4-IgG)血清阳性NMOSD（eculizumab、inebilizumab和satralizumab）的维持治疗，促使需要考虑该适应症的最佳治疗决策实践。我们的目的是通过基于证据的Delphi共识程序，制定经过验证的AQP4-IgG血清阳性NMOSD管理声明，重点关注eculizumab、inebilizumab和 satralizumab的建议。

方法 我们招募了NMOSD的国际临床专家小组，要求他们完成关于NMOSD管理的调查问卷。专家小组成员收到了通过目标文献综述确定的证据总结，并根据提供的数据及其临床经验对问卷进行了自由文本回复。答复被用来产生关于非传染性疾病有关主题的声明草案。发言最多进行3轮投票小组成员匿名提供了他们对每项声明的同意程度（6分Likert量表）。根据反馈对未能达到预定共识阈值(≥67%)的声明进行修订，然后在下一轮进行表决。最终声明是符合共识阈值（≥67%）的声明。

结果 Delphi小组由24名专家组成，他们在2轮投票后于2021年11月完成进程。在第1轮中，23/25的声明达成了共识，并被接受为最终声明。对未能达成共识的2项声明进行了修订。在第二轮中，两份订正声明都达成了共识。共有25项声明达成一致：11项开始或转换为eculizumab、inebilizumab和 satralizumab；7项关于安全性和患者人群的考虑与 AQP4-IgG 血清阳性NMOSD的管理相关。3项关于生物标记物/患者报告的结果；1项为研究偏差。

讨论 使用已经确定的公共方法制定与AQP4-IgG+NMOSD管理相关的声明。这些国际声明将对个体化治疗决策很有价值，并可形成标准化实践指南的基础。