A multicentre study on predictors of relapses in AQP4-IgG NMOSD: Do titres matter?
Abstract
Background Neuromyelitis Optica Spectrum Disorder (NMOSD) is a severe autoimmune-mediated inflammatory condition affecting the central nervous system. While various factors, such as immunotherapy regimens, influence the risk of relapse, the predictive significance of aquaporin-4 immunoglobulin G (AQP4-IgG) status is still debated. Identifying the determinants of disease severity and factors associated with relapse is essential for the development of personalized therapeutic strategies. Objective This study aims to identify risk factors associated with relapse in patients diagnosed with serum AQP4 antibody-positive NMOSD. Additionally, it seeks to examine the impact of various traditional immunotherapy regimens and the different titres of AQP4-IgG on the relapse rates in these patients. Design This retrospective cohort study, conducted across multiple centers, examined longitudinal data from 314 seropositive AQP4-IgG NMOSD patients treated at seven medical centers from January 2014 to June 2024. Methods This study used annualized relapse rate (ARR) as the outcome measure. Kaplan-Meier, logistic regression, and Cox regression were used to assess the risk factors for relapse. The specific titers of AQP4-IgG were classified into different subgroups: negative, low-positive, moderate-positive, and high-positive. The relapse rate was compared among different AQP4-IgG titers and treatment patterns (tacrolimus, mycophenolate mofetil, azathioprine, oral glucocorticoid-only, or no medication). Results We reviewed 314 AQP4-IgG positive (median [IQR] age at onset: 45.0 [33.0, 54.0] years; 86.0% female) NMOSD inpatients and outpatients. The median disease duration was 47 (26, 84) months. The median relapse-free survival period for patients with NMOSD was 30 months. AQP4-IgG seropositive status (OR =6.75,95% CI 2.95-15.46,P<0.001)during the disease course and multisystem involvement at initial onset (OR =1.89,95% CI 1.025-3.486,P = 0.041) were identified as independent risk factors for relapse. Patients who received standardized immunotherapy during remission (OR = 0.05,95% CI 0.02-0.14,P<0.001) demonstrated a significantly reduced risk of relapse. In contrast, the median relapse time for patients treated solely with oral glucocorticoids was comparable to that of untreated controls (HR=0.92, 95% CI 0.68-1.23, P=0.561). Patients who achieved seronegative status during observation exhibited the longest median interval between relapses. Seroconversion to AQP4-IgG negativity (HR=0.40,95%CI 0.21-0.75,P=0.005) during observation was associated with a reduction in both relapse frequency and annualized relapse rate (ARR). Conclusion The implementation of standardized immunotherapy markedly decreased the incidence of relapse in patients with NMOSD. Multisystem involvement at initial onset and AQP4-IgG seropositive status during the course of the disease were predictive of a higher likelihood of relapse.
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BibTeX
@article{zhan2026multicentre,
title = {{A multicentre study on predictors of relapses in AQP4-IgG NMOSD: Do titres matter?}},
author = {Jiayang Zhan and Huizhen Ge and Jinquan Hu and Lijun Luo and Qunhui Liu and Dan He and Daokai Gong and Zhenqiong Hu and Xingyu Han and Xuanxuan Pan and Zhijun Li and Bitao Bu and Mengcui Gui},
journal = {Therapeutic Advances in Neurological Disorders},
year = {2026},
month = oct,
doi = {10.1177/17562864261489410},
url = {https://doi.org/10.1177/17562864261489410},
note = {CC BY},
}
RIS
TY - JOUR
TI - A multicentre study on predictors of relapses in AQP4-IgG NMOSD: Do titres matter?
AU - Jiayang Zhan
AU - Huizhen Ge
AU - Jinquan Hu
AU - Lijun Luo
AU - Qunhui Liu
AU - Dan He
AU - Daokai Gong
AU - Zhenqiong Hu
AU - Xingyu Han
AU - Xuanxuan Pan
AU - Zhijun Li
AU - Bitao Bu
AU - Mengcui Gui
PY - 2026
DA - 2026/10/24
JO - Therapeutic Advances in Neurological Disorders
DO - 10.1177/17562864261489410
UR - https://doi.org/10.1177/17562864261489410
AB - Background Neuromyelitis Optica Spectrum Disorder (NMOSD) is a severe autoimmune-mediated inflammatory condition affecting the central nervous system. While various factors, such as immunotherapy regimens, influence the risk of relapse, the predictive significance of aquaporin-4 immunoglobulin G (AQP4-IgG) status is still debated. Identifying the determinants of disease severity and factors associated with relapse is essential for the development of personalized therapeutic strategies. Objective This study aims to identify risk factors associated with relapse in patients diagnosed with serum AQP4 antibody-positive NMOSD. Additionally, it seeks to examine the impact of various traditional immunotherapy regimens and the different titres of AQP4-IgG on the relapse rates in these patients. Design This retrospective cohort study, conducted across multiple centers, examined longitudinal data from 314 seropositive AQP4-IgG NMOSD patients treated at seven medical centers from January 2014 to June 2024. Methods This study used annualized relapse rate (ARR) as the outcome measure. Kaplan-Meier, logistic regression, and Cox regression were used to assess the risk factors for relapse. The specific titers of AQP4-IgG were classified into different subgroups: negative, low-positive, moderate-positive, and high-positive. The relapse rate was compared among different AQP4-IgG titers and treatment patterns (tacrolimus, mycophenolate mofetil, azathioprine, oral glucocorticoid-only, or no medication). Results We reviewed 314 AQP4-IgG positive (median [IQR] age at onset: 45.0 [33.0, 54.0] years; 86.0% female) NMOSD inpatients and outpatients. The median disease duration was 47 (26, 84) months. The median relapse-free survival period for patients with NMOSD was 30 months. AQP4-IgG seropositive status (OR =6.75,95% CI 2.95-15.46,P<0.001)during the disease course and multisystem involvement at initial onset (OR =1.89,95% CI 1.025-3.486,P = 0.041) were identified as independent risk factors for relapse. Patients who received standardized immunotherapy during remission (OR = 0.05,95% CI 0.02-0.14,P<0.001) demonstrated a significantly reduced risk of relapse. In contrast, the median relapse time for patients treated solely with oral glucocorticoids was comparable to that of untreated controls (HR=0.92, 95% CI 0.68-1.23, P=0.561). Patients who achieved seronegative status during observation exhibited the longest median interval between relapses. Seroconversion to AQP4-IgG negativity (HR=0.40,95%CI 0.21-0.75,P=0.005) during observation was associated with a reduction in both relapse frequency and annualized relapse rate (ARR). Conclusion The implementation of standardized immunotherapy markedly decreased the incidence of relapse in patients with NMOSD. Multisystem involvement at initial onset and AQP4-IgG seropositive status during the course of the disease were predictive of a higher likelihood of relapse.
SN - 1756-2864
SN - 1756-2856
ER -