King's College London

Research portal

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

Research output: Contribution to journalArticlepeer-review

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 & 11 more 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 and

Original languageEnglish
Pages (from-to)1333-1344
Number of pages12
JournalJAMA Neurology
Issue number11
PublishedNov 2021

Bibliographical note

Funding Information: Additional Contributions: This study was supported and endorsed by the Autoimmune Encephalitis Alliance. Thank you to Kimberley de Haseth, BSc (Autoimmune Encephalitis Alliance, Durham, North Carolina), for support and advice. She was not compensated for her contribution. Funding Information: Funding/Support: Dr Eyre is supported by Action Medical Research and the British Paediatric Neurology Association. Dr Molteni is supported by the Medical Research Council Skills Development Fellowship Scheme. Dr Armangue is supported by research grants from Instituto Carlos III/FEDER, Spain (PI18/00486), and Generalitat de Catalunya PERIS (SLT006/17/00362). Dr Irani is supported by the Wellcome Trust (104079/Z/14/Z), the UCB-Oxford University Alliance, BMA Research Grants, Vera Down grant (2013) and Margaret Temple grant (2017), Epilepsy Research UK (P1201), the Fulbright UK-US Commission (Multiple Sclerosis Society research award), and the National Institute for Health Research Oxford Biomedical Research Centre. Dr Dale is supported by National Health and Medical Research Council Investigator grant (Australia) and Petre Foundation. Dr Ming Lim receives research grants from Action Medical Research, the Dancing Eye Syndrome Society, the Great Ormond Street Hospital Charity, the National Institute for Health Research, the Multiple Sclerosis Society UK, and the Sparks Charity; and receives research support grants from the London Clinical Research Network and the Evelina Appeal. Funding Information: research funding from Pfizer and Roche. Dr Neuteboom participates in treatment studies in pediatric multiple sclerosis by Novartis and Sanofi-Genzyme and has received consultation fees from Novartis, Zogenix, and Sanofi-Genzyme. Dr Rostásy participates in treatment studies in pediatric multiple sclerosis by Roche. Dr Tenembaum has received personal fees from Biogen Idec Argentina, Genzyme, Novartis Pharma, Novartis Argentina, Genentech-Roche, and Alexion Pharmaceuticals. Dr Wickstrom has received grants from the Stockholm City Council and Hjärnfonden; consultation fees from Roche, Novartis, and Octapharma; and personal fees from Octapharma, Roche, GW Pharma, and Biogen. Dr Yeshokumar has received personal fees from Bristol Myers Squibb. No other disclosures were reported. Funding Information: received grants from the UK Medical Research Council Fellowship Scheme. Dr Irani has received grants from CSL Behring, UCB Pharma, and Ono Pharmaceutical; personal fees from UCB Pharma and ADC Therapeutics; and is a coapplicant and receives royalties on patent application WO/210/ 046716. Dr Dalmau has received royalties from Euroimmun and grants from SAGE. Dr Ming Lim has received consultation fees from CSL Behring, Novartis, Octapharma, and Roche; grants from Boston Children’s Hospital Research Funds, Great Ormond Street Hospital grant, and Great Ormond Street Hospital/Guy’s and St Thomas’ Trust/ St Mary’s Hospital Charity; and has received travel grants from Merck Serono; and was awarded educational grants to organize meetings by Novartis, Biogen Idec, Merck Serono, and Bayer. Dr Armangue has received personal fees from Biogen and Novartis. Dr Cellucci has received personal fees from Novartis Canada. Dr Deiva has received personal fees from Novartis, Biogen, Sanofi, and Viela and nonfinancial support from Novartis. Dr Gombolay receives part-time salary support from the US Centers for Disease Control and Prevention to review acute flaccid myelitis cases for surveillance. Dr Gorman has received Publisher Copyright: © 2021 American Medical Association. All rights reserved.

King's Authors


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..

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454