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A real-world study of interleukin-6 receptor blockade in patients with neuromyelitis optica spectrum disorder

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Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune disease that can cause permanent neurological disabilities. However, the interleukin-6 (IL-6) signaling pathway is a promising therapeutic target for relapse prevention. Therefore, this study evaluated the long-term effectiveness of tocilizumab, a humanized anti-IL-6 receptor antibody, for NMOSD. We enrolled 65 patients with NMOSD who received regular intravenous administration of tocilizumab (8 mg/kg) between October 2017 and January 2022. Then, we retrospectively collected data on the clinical characteristics and baseline glial fibrillary acidic protein (GFAP) and neurofilament light chain levels. The primary outcome was the annualized relapse rate (ARR). Risk factors were assessed using a multivariable logistic regression model. During the median follow-up of 34.1 (interquartile range: 25.5–39.3) months, 23% (15/65) of patients relapsed during tocilizumab treatment, but the median ARR decreased from 1.9 (range 0.12–6.29) to 0.1 (range 0–1.43, p < 0.0001). A prolonged infusion interval (> 4 weeks, odds ratio [OR]: 10.7, 95% confidence interval [CI]: 1.6–71.4, p = 0.014) and a baseline plasma GFAP level of > 220 pg/mL (OR: 20.6, 95% CI 3.3–129.4, p  = 0.001) were risk factors for future relapses. During treatment, the median Expanded Disability Status Scale score significantly decreased in aquaporin-4 antibody-positive and -negative patients, but the pain did not considerably improve. There were no severe safety concerns. Tocilizumab treatment significantly reduced the relapse rate in patients with NMOSD. However, prolonged infusion intervals and high baseline plasma GFAP levels may increase the relapse risk during tocilizumab therapy.

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Acknowledgements

We thank the patients, doctors, and nurses from the Department of Neurology, Tianjin Medical University General Hospital, who participated in this study and all members of the Jing-Jin Center for Neuroinflammation for their support.

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Authors and Affiliations

  1. Department of Neurology and Institute of Neuroimmunology, Tianjin Medical University General Hospital, Tianjin, China

    Shu Yang, Chen Zhang, Tian-Xiang Zhang, Bin Feng, Dongmei Jia, Shasha Han, Ting Li, Yi Shen, Guangxun Yan & Chao Zhang

  2. Centers of Neuroimmunology and Neurological Diseases, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Chao Zhang

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  1. Shu Yang
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  2. Chen Zhang
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Contributions

CZ conceptualized and designed the study. SY, CZ, TXZ, BF, DJ, SH, TL, and GY performed the experiments. SY, TXZ, and DJ analyzed the results. LY, QL, and FDS supervised the study. SY and CZ wrote and edited the manuscript.

Corresponding author

Correspondence to Chao Zhang.

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Conflicts of interest

The study was supported by the National Natural Science Foundation of China (grant no. 82171777 to C.Z.) and the Natural Science Foundation of Tianjin Province (grant no. 20JCJQJC00280 to C.Z.)

Standard protocol approval, registration, and patient consent

The Institutional Review Board of Tianjin Medical University General Hospital provided ethical approval based on the ICH–Good Clinical Practice guidelines. All patients provided written informed consent.

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Yang, S., Zhang, C., Zhang, TX. et al. A real-world study of interleukin-6 receptor blockade in patients with neuromyelitis optica spectrum disorder. J Neurol 270, 348–356 (2023). https://doi.org/10.1007/s00415-022-11364-9

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  • DOI: https://doi.org/10.1007/s00415-022-11364-9

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