Siriratnam Pakeeran, Sanfilippo Paul, van der Walt Anneke, Sharmin Sifat, Foong Yi Chao, Yeh Wei Zhen, Zhu Chao, Khoury Samia Joseph, Csepany Tunde, Willekens Barbara, Etemadifar Masoud, Ozakbas Serkan, Nytrova Petra, Altintas Ayse, Al-Asmi Abdullah, Yamout Bassem, Laureys Guy, Patti Francesco, Simo Magdolna, Surcinelli Andrea, Foschi Matteo, McCombe Pamela A, Alroughani Raed, Sánchez-Menoyo José Luis, Turkoglu Recai, Soysal Aysun, Lechner Scott Jeanette, Kalincik Tomas, Butzkueven Helmut, Jokubaitis Vilija, Huda Saif, Monif Mastura
Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
Alfred Health, Department of Neurology, Melbourne, Victoria, Australia.
J Neurol Neurosurg Psychiatry. 2025 Mar 24;96(4):361-369. doi: 10.1136/jnnp-2024-334090.
Neuromyelitis optica spectrum disorder (NMOSD) can be categorised into aquaporin-4 antibody (AQP4-IgG) NMOSD or seronegative NMOSD. While our knowledge of AQP4-IgG NMOSD has evolved significantly in the past decade, seronegative NMOSD remains less understood. This study aimed to evaluate the predictors of relapses and treatment responses in AQP4-IgG NMOSD and seronegative NMOSD.
This was a multicentre, international, retrospective cohort study using the MSBase registry. Recurrent relapse risk was assessed using an Andersen-Gill model and risk of first relapse was evaluated using a Cox proportional hazards model. Covariates that putatively influence relapse risk included demographic factors, clinical characteristics and immunosuppressive therapies; the latter was assessed as a time-varying covariate.
A total of 398 patients (246 AQP4-IgG NMOSD and 152 seronegative NMOSD) were included. The AQP4-IgG NMOSD and seronegative NMOSD patients did not significantly differ by age at disease onset, ethnicity or annualised relapse rate. Both low-efficacy and high-efficacy immunosuppressive therapies were associated with significant reductions in recurrent relapse risk, with notably greater protection conferred by high-efficacy therapies in both AQP4-IgG NMOSD (HR 0.27, 95% CI 0.15 to 0.49, p<0.001) and seronegative NMOSD (HR 0.21, 95% CI 0.08 to 0.51, p<0.001). Longer disease duration (HR 0.97, 95% CI 0.95 to 0.99, p<0.001) and male sex (HR 0.52, 95% CI 0.34 to 0.84, p=0.007) were additional protective variables in reducing the recurrent relapse risk for the AQP4-IgG NMOSD group.
Although further studies are needed to improve our understanding of seronegative NMOSD, our findings underscore the importance of aggressive treatment with high-efficacy immunotherapies in both NMOSD subtypes, regardless of serostatus.
视神经脊髓炎谱系障碍（NMOSD）可分为水通道蛋白4抗体（AQP4-IgG）NMOSD或血清阴性NMOSD。尽管在过去十年中我们对AQP4-IgG NMOSD的认识有了显著进展，但血清阴性NMOSD仍了解较少。本研究旨在评估AQP4-IgG NMOSD和血清阴性NMOSD复发及治疗反应的预测因素。
这是一项使用MSBase注册库的多中心、国际性回顾性队列研究。使用Andersen-Gill模型评估复发风险，使用Cox比例风险模型评估首次复发风险。可能影响复发风险的协变量包括人口统计学因素、临床特征和免疫抑制治疗；后者作为随时间变化的协变量进行评估。
共纳入398例患者（246例AQP4-IgG NMOSD和152例血清阴性NMOSD）。AQP4-IgG NMOSD和血清阴性NMOSD患者在疾病发病年龄、种族或年化复发率方面无显著差异。低效和高效免疫抑制治疗均与复发风险显著降低相关，高效治疗在AQP4-IgG NMOSD（HR 0.27，95%CI 0.15至0.49，p<0.001）和血清阴性NMOSD（HR 0.21，95%CI 0.08至0.51，p<0.001）中均提供了更显著的保护作用。病程较长（HR 0.97, 95%CI 0.95至0.99，p<0.001）和男性（HR 0.52，95%CI 0.34至0.84，p=0.007）是降低AQP4-IgG NMOSD组复发风险的额外保护变量。
尽管需要进一步研究以加深我们对血清阴性NMOSD的理解，但我们的研究结果强调了在两种NMOSD亚型中积极使用高效免疫疗法进行治疗的重要性，无论血清学状态如何。
