TY - JOUR
T1 - Predictors of relapse risk and treatment response in AQP4-IgG positive and seronegative NMOSD
T2 - A multicentre study
AU - Siriratnam, Pakeeran
AU - Sanfilippo, Paul
AU - van der Walt, Anneke
AU - Sharmin, Sifat
AU - Foong, Yi Chao
AU - Yeh, Wei Zhen
AU - Zhu, Chao
AU - Khoury, Samia Joseph
AU - Csepany, Tunde
AU - Willekens, Barbara
AU - Etemadifar, Masoud
AU - Ozakbas, Serkan
AU - Nytrova, Petra
AU - Altintas, Ayse
AU - Al-Asmi, Abdullah
AU - Yamout, Bassem
AU - Laureys, Guy
AU - Patti, Francesco
AU - Simo, Magdolna
AU - Surcinelli, Andrea
AU - Foschi, Matteo
AU - McCombe, Pamela A.
AU - Alroughani, Raed
AU - Sánchez-Menoyo, José Luis
AU - Turkoglu, Recai
AU - Soysal, Aysun
AU - Scott, Jeanette Lechner
AU - Kalincik, Tomas
AU - Butzkueven, Helmut
AU - Jokubaitis, Vilija
AU - Huda, Saif
AU - Monif, Mastura
AU - MSBase Study Group
AU - Horakova, Dana
AU - Van Hijfte, Liesbeth
AU - Boz, Cavit
AU - Shalaby, Nevin
AU - Grand'Maison, Francois
AU - Mario,
AU - Habek,
AU - Singhal, Bhim
AU - Hodgkinson, Suzanne
AU - Buzzard, Katherine
AU - Skibina, Olga
AU - Slee, Mark
AU - Alkhaboori, Jabir
AU - Inshasi, Jihad
AU - Lapointe, Emmanuelle
AU - Boggild, Mike
AU - Vucic, Steve
AU - Gray, Orla
AU - Khurana, Dheeraj
AU - Amato, Maria Pia
AU - Cristiano, Edgardo
AU - Liu, Yaou
AU - Cartechini, Elisabetta
AU - Al-Harbi, Talal
AU - Hardy, Todd
PY - 2025/4
Y1 - 2025/4
N2 - 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.
AB - 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.
KW - Neuromyelitis optica spectrum disorder
KW - NMOSD
KW - autoimmune
KW - central nervous system
KW - CNS
KW - heterogeneous disease
UR - https://www.scopus.com/pages/publications/85204235831
U2 - 10.1136/jnnp-2024-334090
DO - 10.1136/jnnp-2024-334090
M3 - Article
C2 - 39231582
AN - SCOPUS:85204235831
SN - 0022-3050
VL - 96
SP - 361
EP - 369
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
IS - 4
ER -