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Nosadini M, Eyre M, Molteni E, et al. Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis. JAMA Neurol. 2021;78(11):1333-1344doi: 10.1001/jamaneurol.2021.3188.
Nosadini, M., Eyre, M., Molteni, E., Thomas, T., Irani, S. R., Dalmau, J., Dale, R. C., Lim, M., Anlar, B., Armangue, T., Benseler, S., Cellucci, T., Deiva, K., Gallentine, W., Gombolay, G., Gorman, M. P., Hacohen, Y., Jiang, Y., Lim, B. C., Muscal, E., Ndondo, A., Neuteboom, R., Rostásy, K., Sakuma, H., Sartori, S., Sharma, S., Tenembaum, S. N., Van Mater, H. A., Wells, E., Wickstrom, R., & Yeshokumar, A. K. (2021). Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis. JAMA neurology, 78(11), 1333-1344. https://doi.org/10.1001/jamaneurol.2021.3188
Nosadini, Margherita, et al. "Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis." JAMA neurology vol. 78,11 (2021): 1333-1344. doi: https://doi.org/10.1001/jamaneurol.2021.3188
Nosadini M, Eyre M, Molteni E, Thomas T, Irani SR, Dalmau J, Dale RC, Lim M, Anlar B, Armangue T, Benseler S, Cellucci T, Deiva K, Gallentine W, Gombolay G, Gorman MP, Hacohen Y, Jiang Y, Lim BC, Muscal E, Ndondo A, Neuteboom R, Rostásy K, Sakuma H, Sartori S, Sharma S, Tenembaum SN, Van Mater HA, Wells E, Wickstrom R, Yeshokumar AK. Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis. JAMA Neurol. 2021 Nov 01;78(11):1333-1344. doi: 10.1001/jamaneurol.2021.3188. PMID: 34542573; PMCID: PMC8453367.
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JAMA Neurol. 2021 Nov 01;78(11):1333-1344. doi: 10.1001/jamaneurol.2021.3188.

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis.

JAMA neurology

Margherita Nosadini, Michael Eyre, Erika Molteni, Terrence Thomas, Sarosh R Irani, Josep Dalmau, Russell C Dale, Ming Lim, Banu Anlar, Thaís Armangue, Susanne Benseler, Tania Cellucci, Kumaran Deiva, William Gallentine, Grace Gombolay, Mark P Gorman, Yael Hacohen, Yuwu Jiang, Byung Chan Lim, Eyal Muscal, Alvin Ndondo, Rinze Neuteboom, Kevin Rostásy, Hiroshi Sakuma, Stefano Sartori, Suvasini Sharma, Silvia Noemi Tenembaum, Heather Ann Van Mater, Elizabeth Wells, Ronny Wickstrom, Anusha K Yeshokumar

Affiliations

  1. Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padova, Padova, Italy.
  2. Neuroimmunology Group, Paediatric Research Institute "Città della Speranza," Padova, Italy.
  3. School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom.
  4. Children's Neurosciences, Evelina London Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
  5. Centre for Medical Engineering, King's College London, London, United Kingdom.
  6. Department of Paediatrics, Neurology Service, KK Women's and Children's Hospital, Singapore.
  7. Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
  8. Department of Neurology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
  9. Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain.
  10. Department of Neurology, University of Pennsylvania, Philadelphia.
  11. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
  12. Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Westmead, Australia.
  13. Department of Women and Children's Health, School of Life Course Sciences (SoLCS), King's College London, London, United Kingdom.
  14. Hacettepe University, Ankara, Turkey.
  15. Sant Joan de Déu (SJD) Children's Hospital, University of Barcelona, Barcelona, Spain.
  16. Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
  17. McMaster University, Hamilton, Ontario, Canada.
  18. Assistance Publique-Hôpitaux de Paris, University Hospitals Paris Saclay, Bicêtre Hospital, Paris, France.
  19. French Reference Network of Rare Inflammatory Brain and Spinal Diseases, Paris, France.
  20. European Reference Network-RITA, Paris, France.
  21. Stanford University and Lucile Packard Children's Hospital, Palo Alto, California.
  22. Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
  23. Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
  24. Queen Square MS Centre, UCL Institute of Neurology, University College London, London, United Kingdom.
  25. Department of Paediatric Neurology, Great Ormond Street Hospital for Children, London, United Kingdom.
  26. Peking University First Hospital, Beijing, China.
  27. Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
  28. Section Rheumatology, Texas Children's Hospital, Baylor College of Medicine, Houston.
  29. Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
  30. Faculty of Health Sciences, University of Cape Town Neuroscience Institute, Cape Town, South Africa.
  31. Erasmus Medical Center, Rotterdam, the Netherlands.
  32. Children's Hospital Datteln, University Witten/Herdecke, Witten, Germany.
  33. Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
  34. University Hospital of Padova, Padova, Italy.
  35. Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India.
  36. National Pediatric Hospital Dr J. Garrahan, Buenos Aires, Argentina.
  37. Duke University, Durham, North Carolina.
  38. Children's National Medical Center, Washington, DC.
  39. Karolinska University Hospital, Stockholm, Sweden.
  40. Icahn School of Medicine at Mount Sinai, New York, New York.

PMID: 34542573 PMCID: PMC8453367 DOI: 10.1001/jamaneurol.2021.3188

Abstract

IMPORTANCE: Overall, immunotherapy has been shown to improve outcomes and reduce relapses in individuals with N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis (NMDARE); however, the superiority of specific treatments and combinations remains unclear.

OBJECTIVE: To map the use and safety of immunotherapies in individuals with NMDARE, identify early predictors of poor functional outcome and relapse, evaluate changes in immunotherapy use and disease outcome over the 14 years since first reports of NMDARE, and assess the Anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score.

DATA SOURCES: Systematic search in PubMed from inception to January 1, 2019.

STUDY SELECTION: Published articles including patients with NMDARE with positive NMDAR antibodies and available individual immunotherapy data.

DATA EXTRACTION AND SYNTHESIS: Individual patient data on immunotherapies, clinical characteristics at presentation, disease course, and final functional outcome (modified Rankin Scale [mRS] score) were entered into multivariable logistic regression models.

MAIN OUTCOMES AND MEASURES: The planned study outcomes were functional outcome at 12 months from disease onset (good, mRS score of 0 to 2; poor, mRS score greater than 2) and monophasic course (absence of relapse at 24 months or later from onset).

RESULTS: Data from 1550 patients from 652 articles were evaluated. Of these, 1105 of 1508 (73.3%) were female and 707 of 1526 (46.3%) were 18 years or younger at disease onset. Factors at first event that were significantly associated with good functional outcome included adolescent age and first-line treatment with therapeutic apheresis, corticosteroids plus intravenous immunoglobulin (IVIG), or corticosteroids plus IVIG plus therapeutic apheresis. Factors significantly associated with poor functional outcome were age younger than 2 years or age of 65 years or older at onset, intensive care unit admission, extreme delta brush pattern on electroencephalography, lack of immunotherapy within the first 30 days of onset, and maintenance IVIG use for 6 months or more. Factors significantly associated with nonrelapsing disease were rituximab use or maintenance IVIG use for 6 months or more. Adolescent age at onset was significantly associated with relapsing disease. Rituximab use increased from 13.5% (52 of 384; 2007 to 2013) to 28.3% (311 of 1100; 2013 to 2019) (P < .001), concurrent with a falling relapse rate over the same period (22% [12 of 55] in 2008 and earlier; 10.9% [35 of 322] in 2017 and later; P = .006). Modified NEOS score (including 4 of 5 original NEOS items) was associated with probability of poor functional status at 1 year (20.1% [40 of 199] for a score of 0 to 1 points; 43.8% [77 of 176] for a score of 3 to 4 points; P = .05).

CONCLUSIONS AND RELEVANCE: Factors influencing functional outcomes and relapse are different and need to be considered independently in development of evidence-based optimal management guidelines of patients with NMDARE.

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