Predictors of Relapse Risk and Treatment Response in Aqp4-Igg Positive and Seronegative Nmosd: A Multicentre Study Publisher Pubmed



Siriratnam P^{1, 2, 3} ; Sanfilippo P^{1, 2} ; Van Der Walt A^{1, 2} ; Sharmin S⁴ ; Foong YC^{1, 5} ; Yeh WZ^{1, 2} ; Zhu C¹ ; Khoury SJ^{6, 7} ; Csepany T⁸ ; Willekens B^{9, 10} ; Etemadifar M^{11, 12} ; Ozakbas S^{13, 14} ; Nytrova P¹⁵ ; Altintas A¹⁶ Show All Authors Show Affiliations
Source: Journal of Neurology, Neurosurgery and Psychiatry Published:2024

Abstract

Background 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. Methods This was a multicentre, international, retrospective cohort study using the MSBase registry. Recurrent relapse risk was assessed using an AndersenGill 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. Results A total of 398 patients (246 AQP4-IgG NMOSD and 152seronegative 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 highefficacy 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. Conclusion 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. © Author(s) (or their employer(s)) 2024.