PMID- 34542573 OWN - NLM STAT- MEDLINE DCOM- 20220114 LR - 20220324 IS - 2168-6157 (Electronic) IS - 2168-6149 (Print) IS - 2168-6149 (Linking) VI - 78 IP - 11 DP - 2021 Nov 1 TI - Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis. PG - 1333-1344 LID - 10.1001/jamaneurol.2021.3188 [doi] AB - 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. FAU - Nosadini, Margherita AU - Nosadini M AD - Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padova, Padova, Italy. AD - Neuroimmunology Group, Paediatric Research Institute "Citta della Speranza," Padova, Italy. FAU - Eyre, Michael AU - Eyre M AD - School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom. AD - Children's Neurosciences, Evelina London Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. FAU - Molteni, Erika AU - Molteni E AD - School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom. AD - Centre for Medical Engineering, King's College London, London, United Kingdom. FAU - Thomas, Terrence AU - Thomas T AD - Department of Paediatrics, Neurology Service, KK Women's and Children's Hospital, Singapore. FAU - Irani, Sarosh R AU - Irani SR AD - Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom. AD - Department of Neurology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. FAU - Dalmau, Josep AU - Dalmau J AD - Neuroimmunology Program, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain. AD - Department of Neurology, University of Pennsylvania, Philadelphia. AD - Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Spain. FAU - Dale, Russell C AU - Dale RC AD - Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Westmead, Australia. FAU - Lim, Ming AU - Lim M AD - Children's Neurosciences, Evelina London Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. AD - Department of Women and Children's Health, School of Life Course Sciences (SoLCS), King's College London, London, United Kingdom. CN - International NMDAR Antibody Encephalitis Consensus Group FAU - Anlar, Banu AU - Anlar B AD - Hacettepe University, Ankara, Turkey. FAU - Armangue, Thais AU - Armangue T AD - Neuroimmunology Program, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain. AD - Sant Joan de Deu (SJD) Children's Hospital, University of Barcelona, Barcelona, Spain. FAU - Benseler, Susanne AU - Benseler S AD - Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. FAU - Cellucci, Tania AU - Cellucci T AD - McMaster University, Hamilton, Ontario, Canada. FAU - Deiva, Kumaran AU - Deiva K AD - Assistance Publique-Hopitaux de Paris, University Hospitals Paris Saclay, Bicetre Hospital, Paris, France. AD - French Reference Network of Rare Inflammatory Brain and Spinal Diseases, Paris, France. AD - European Reference Network-RITA, Paris, France. FAU - Gallentine, William AU - Gallentine W AD - Stanford University and Lucile Packard Children's Hospital, Palo Alto, California. FAU - Gombolay, Grace AU - Gombolay G AD - Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia. FAU - Gorman, Mark P AU - Gorman MP AD - Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Hacohen, Yael AU - Hacohen Y AD - Queen Square MS Centre, UCL Institute of Neurology, University College London, London, United Kingdom. AD - Department of Paediatric Neurology, Great Ormond Street Hospital for Children, London, United Kingdom. FAU - Jiang, Yuwu AU - Jiang Y AD - Peking University First Hospital, Beijing, China. FAU - Lim, Byung Chan AU - Lim BC AD - Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Muscal, Eyal AU - Muscal E AD - Section Rheumatology, Texas Children's Hospital, Baylor College of Medicine, Houston. FAU - Ndondo, Alvin AU - Ndondo A AD - Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa. AD - Faculty of Health Sciences, University of Cape Town Neuroscience Institute, Cape Town, South Africa. FAU - Neuteboom, Rinze AU - Neuteboom R AD - Erasmus Medical Center, Rotterdam, the Netherlands. FAU - Rostasy, Kevin AU - Rostasy K AD - Children's Hospital Datteln, University Witten/Herdecke, Witten, Germany. FAU - Sakuma, Hiroshi AU - Sakuma H AD - Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. FAU - Sartori, Stefano AU - Sartori S AD - Neuroimmunology Group, Paediatric Research Institute "Citta della Speranza," Padova, Italy. AD - University Hospital of Padova, Padova, Italy. FAU - Sharma, Suvasini AU - Sharma S AD - Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India. FAU - Tenembaum, Silvia Noemi AU - Tenembaum SN AD - National Pediatric Hospital Dr J. Garrahan, Buenos Aires, Argentina. FAU - Van Mater, Heather Ann AU - Van Mater HA AD - Duke University, Durham, North Carolina. FAU - Wells, Elizabeth AU - Wells E AD - Children's National Medical Center, Washington, DC. FAU - Wickstrom, Ronny AU - Wickstrom R AD - Karolinska University Hospital, Stockholm, Sweden. FAU - Yeshokumar, Anusha K AU - Yeshokumar AK AD - Icahn School of Medicine at Mount Sinai, New York, New York. LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - MR/V007173/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Neurol JT - JAMA neurology JID - 101589536 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (Immunologic Factors) RN - 4F4X42SYQ6 (Rituximab) SB - IM MH - Adrenal Cortex Hormones/therapeutic use MH - Anti-N-Methyl-D-Aspartate Receptor Encephalitis/*therapy MH - Blood Component Removal/methods MH - Female MH - Humans MH - Immunoglobulins, Intravenous/therapeutic use MH - Immunologic Factors/therapeutic use MH - Immunotherapy/*methods MH - Male MH - Rituximab/therapeutic use PMC - PMC8453367 COIS- Conflict of Interest Disclosures: Dr Molteni has 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 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 Rostasy 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 Hjarnfonden; 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. EDAT- 2021/09/21 06:00 MHDA- 2022/01/15 06:00 PMCR- 2021/09/20 CRDT- 2021/09/20 12:24 PHST- 2021/09/21 06:00 [pubmed] PHST- 2022/01/15 06:00 [medline] PHST- 2021/09/20 12:24 [entrez] PHST- 2021/09/20 00:00 [pmc-release] AID - 2784410 [pii] AID - noi210058 [pii] AID - 10.1001/jamaneurol.2021.3188 [doi] PST - ppublish SO - JAMA Neurol. 2021 Nov 1;78(11):1333-1344. doi: 10.1001/jamaneurol.2021.3188.