Effects of immunotherapies and prognostic predictors in neuromyelitis optica spectrum disorder: a prospective cohort study

  • Ziyan Shi
  • Qin Du
  • Hongxi Chen
  • Ying Zhang
  • Yuhan Qiu
  • Zhengyang Zhao
  • Jiancheng Wang
  • Chao Yan
  • Qin Zhang
  • Mu Yang
  • Hongyu ZhouEmail author
Original Communication



Neuromyelitis optica spectrum disorder (NMOSD), a relapsing autoimmune demyelinating disease of the CNS, often leads to severe visual and/or motor disability. This study aimed to evaluate the long-term effects of the first-line immunotherapies on relapse and disability, and identify the prognostic predictors in NMOSD.


In this prospective cohort study, we enrolled patients with NMOSD from Southwest China and performed a long-term follow-up. We compared no immunotherapies (NIT) versus treatment of mycophenolate mofetil (MMF), azathioprine (AZA), or only corticosteroid (CS). Cox proportional-hazards model was used to explore the prognostic predictors in NMOSD.


Ultimately, 281 patients were enrolled during 2009 to 2017. The proportions of relapse, motor disability, and mortality were significantly lower in treatments of MMF and AZA than in NIT (all P < 0.001), while no significant difference was found between the CS and NIT groups. The multivariate Cox analyses indicated that onset with optic neuritis and increased age at onset were risk predictors of visual disability and motor disability, respectively. Comparing with NIT, MMF and AZA were remarkably reduced risk of relapse and motor disability but not visual disability. Additionally, median time to first relapse and motor disability was significantly longer in treatments of MMF and AZA than in NIT (both P < 0.001). Furthermore, we estimated the risk of relapse and disability for AQP4-Abs positive NMOSD in 1–5 years based on prognostic predictors identified above.


Our study revealed the potential predictors of relapse and disability, and strengthened evidence that early immunosuppressive treatments, such as MMF and AZA, could effectively reduce the risk of relapse and disability, and delayed progression of NMOSD.


Nueromyelitis optica spectrum disorders NMOSD Mycophenolate mofetil Azathioprine Outcomes Predictors 



This work was supported by the National Key R&D Program of China (Grant No. 2017YFC0907704), the National Natural Science Foundation of China (Grant No. 81801202), and the Department of Science and Technology of Sichuan Province (Grant No. 2018SZ0388). We are very grateful to Mr. Chennan Wang (University of Electronic Science and Technology of China, Chengdu, China) and Dr. Xiaomeng Liu (Sichuan Cancer Hospital and Research Institute, Sichuan Cancer Center, Chengdu, China) for their important contributions to the statistical analysis and revision of our manuscript. We also thank Dr. Zhiyun Lian (Chongqing City Hospital of Traditional Chinese Medicine, Chongqing, China), Dr. Ju Liu (the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China), and Dr. Huiru Feng (Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, Chengdu, Sichuan, China) for their contributions to data collection and follow-up of patients. Finally, we appreciate all of participants in this study for their supports.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflicts of interest, including relevant financial interests, activities, relationships, or affiliations.

Ethical approval

This study was approved by the Medical Ethics Committee of West China Hospital, Sichuan University and was performed in accordance with the ethical standards of the Declaration of Helsinki (approval number: 2018-29). All participants provided informed consent prior to their inclusion in this study.

Supplementary material

415_2019_9649_MOESM1_ESM.doc (674 kb)
Supplementary file1 (DOC 674 kb)


  1. 1.
    Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG (2006) Revised diagnostic criteria for neuromyelitis optica. Neurology 66:1485–1489CrossRefGoogle Scholar
  2. 2.
    Wingerchuk DM, Banwell B, Bennett JL et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85:177–189CrossRefGoogle Scholar
  3. 3.
    Kim SM, Waters P, Woodhall M et al (2013) Utility of aquaporin-4 antibody assay in patients with neuromyelitis optica spectrum disorders. Mult Scler 19:1060–1067CrossRefGoogle Scholar
  4. 4.
    Pandit L, Asgari N, Apiwattanakul M et al (2015) Demographic and clinical features of neuromyelitis optica: a review. Mult Scler 21:845–853CrossRefGoogle Scholar
  5. 5.
    Houzen H, Kondo K, Niino M et al (2017) Prevalence and clinical features of neuromyelitis optica spectrum disorders in northern Japan. Neurology 89:1995–2001CrossRefGoogle Scholar
  6. 6.
    Papp V, Illes Z, Magyari M et al (2018) Nationwide prevalence and incidence study of neuromyelitis optica spectrum disorder in Denmark. Neurology 91:e2265–e2275CrossRefGoogle Scholar
  7. 7.
    Bukhari W, Prain KM, Waters P et al (2017) Incidence and prevalence of NMOSD in Australia and New Zealand. J Neurol Neurosurg Psychiatry 88:632–638CrossRefGoogle Scholar
  8. 8.
    Bruscolini A, Sacchetti M, La Cava M et al (2018) Diagnosis and management of neuromyelitis optica spectrum disorders—an update. Autoimmun Rev 17:195–200CrossRefGoogle Scholar
  9. 9.
    Huh SY, Kim SH, Hyun JW et al (2014) Mycophenolate mofetil in the treatment of neuromyelitis optica spectrum disorder. JAMA Neurol 71:1372–1378CrossRefGoogle Scholar
  10. 10.
    Nikoo Z, Badihian S, Shaygannejad V, Asgari N, Ashtari F (2017) Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder: a randomized clinical trial. J Neurol 264:2003–2009CrossRefGoogle Scholar
  11. 11.
    Huang Q, Wang J, Zhou Y et al (2018) Low-dose mycophenolate mofetil for treatment of neuromyelitis optica spectrum disorders: a prospective multicenter study in South China. Front Immunol 9:2066CrossRefGoogle Scholar
  12. 12.
    Bichuetti DB, Perin M, Souza NA, Oliveira E (2018) Treating neuromyelitis optica with azathioprine: 20-year clinical practice. Mult Scler 25(8):1150–1161CrossRefGoogle Scholar
  13. 13.
    Mealy MA, Wingerchuk DM, Palace J, Greenberg BM, Levy M (2014) Comparison of relapse and treatment failure rates among patients with neuromyelitis optica: multicenter study of treatment efficacy. JAMA Neurol 71:324–330CrossRefGoogle Scholar
  14. 14.
    Stellmann JP, Krumbholz M, Friede T et al (2017) Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response. J Neurol Neurosurg Psychiatry 88:639–647CrossRefGoogle Scholar
  15. 15.
    Kitley J, Leite MI, Nakashima I et al (2012) Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain 135:1834–1849CrossRefGoogle Scholar
  16. 16.
    Kim SH, Hyun JW, Joung A et al (2017) Predictors of response to first-line immunosuppressive therapy in neuromyelitis optica spectrum disorders. Mult Scler 23:1902–1908CrossRefGoogle Scholar
  17. 17.
    Mandler RN, Ahmed W, Dencoff JE (1998) Devic's neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology 51:1219–1220CrossRefGoogle Scholar
  18. 18.
    Jacob A, Matiello M, Weinshenker BG et al (2009) Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective analysis of 24 patients. Arch Neurol 66:1128–1133CrossRefGoogle Scholar
  19. 19.
    Costanzi C, Matiello M, Lucchinetti CF et al (2011) Azathioprine: tolerability, efficacy, and predictors of benefit in neuromyelitis optica. Neurology 77:659–666CrossRefGoogle Scholar
  20. 20.
    Chen H, Qiu W, Zhang Q et al (2017) Comparisons of the efficacy and tolerability of mycophenolate mofetil and azathioprine as treatments for neuromyelitis optica and neuromyelitis optica spectrum disorder. Eur J Neurol 24:219–226CrossRefGoogle Scholar
  21. 21.
    Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452CrossRefGoogle Scholar
  22. 22.
    Jarius S, Probst C, Borowski K et al (2010) Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J Neurol Sci 291:52–56CrossRefGoogle Scholar
  23. 23.
    Mariotto S, Ferrari S, Gastaldi M et al (2019) Neurofilament light chain serum levels reflect disease severity in MOG-Ab associated disorders. J Neurol Neurosurg Psychiatry 90:1293–1296CrossRefGoogle Scholar
  24. 24.
    Jeong IH, Park B, Kim SH et al (2016) Comparative analysis of treatment outcomes in patients with neuromyelitis optica spectrum disorder using multifaceted endpoints. Mult Scler 22:329–339CrossRefGoogle Scholar
  25. 25.
    Kim SH, Mealy MA, Levy M et al (2018) Racial differences in neuromyelitis optica spectrum disorder. Neurology 91:e2089–e2099CrossRefGoogle Scholar
  26. 26.
    Cameron DP, Jonas K, Paul Z, Ben K, Andrew FG, Abdeali JK, Rendeiro AF (2019) CamDavidsonPilon/lifelines: v0.22.10 (Version v0.22.10). Zenodo. doi: 10.5281/zenodo.3533087.Google Scholar
  27. 27.
    Elsone L, Kitley J, Luppe S et al (2014) Long-term efficacy, tolerability and retention rate of azathioprine in 103 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients: a multicentre retrospective observational study from the UK. Mult Scler 20:1533–1540CrossRefGoogle Scholar
  28. 28.
    Palace J, Lin DY, Zeng D et al (2019) Outcome prediction models in AQP4-IgG positive neuromyelitis optica spectrum disorders. Brain 42(5):1310–1323CrossRefGoogle Scholar
  29. 29.
    Kang H, Chen T, Li H et al (2017) Prognostic factors and disease course in aquaporin-4 antibody-positive Chinese patients with acute optic neuritis. J Neurol 264:2130–2140CrossRefGoogle Scholar
  30. 30.
    Collongues N, Marignier R, Jacob A et al (2014) Characterization of neuromyelitis optica and neuromyelitis optica spectrum disorder patients with a late onset. Mult Scler 20:1086–1094CrossRefGoogle Scholar
  31. 31.
    Cabre P, Gonzalez-Quevedo A, Bonnan M et al (2009) Relapsing neuromyelitis optica: long term history and clinical predictors of death. J Neurol Neurosurg Psychiatry 80:1162–1164CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurology, West China HospitalSichuan UniversityChengduChina
  2. 2.Department of NeurologyZigong Fourth Peoples HospitalZigongChina
  3. 3.Sichuan Cancer Hospital and Research InstituteSichuan Cancer CenterChengduChina

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