Multicenter Study

. 2025 Jul;12(4):e200395.

doi: 10.1212/NXI.0000000000200395. Epub 2025 May 30.

Rituximab Use for Relapse Prevention in Anti-NMDAR Antibody-Mediated Encephalitis: A Multicenter Cohort Study

Nabil Seery^{1

2}, Robb Wesselingh^{1

2}, Paul Beech^{3

4}, Laurie McLaughlin^{5

6}, Tiffany Rushen^{1

2}, Amy J Halliday⁷, Liora Ter Horst^{5

6}, Sarah P Griffith^{1

2}, Mirasol Forcadela⁸, Tracie H Tan^{1

2}, Christina Kazzi^{1

2}, Cassie Nesbitt^{2

9}, James Broadley^{1

2}, Katherine Buzzard¹⁰, Andrew Duncan⁷, Wendyl J D'Souza⁷, Yang Tran^{7

11}, Anneke Van Der Walt^{1

2}, Genevieve Skinner^{5

6}, Bruce V Taylor¹², Andrew Swayne^{5

6}, Amy Brodtmann^{1

10

13}, David Gillis¹⁴, Ernest Gerard Butler¹⁵, Tomas Kalincik^{16

17}, Udaya K Seneviratne^{1

7

18}, Richard A Macdonell⁸, Stefan Blum^{5

6}, Sudarshini Ramanathan^{19

20}, Charles B Malpas^{1

21

22}, Stephen W Reddel^{19

23}, Todd A Hardy^{19

23}, Terence J O'Brien^{1

2}, Paul G Sanfilippo¹, Helmut Butzkueven^{1

2}, Mastura Monif^{1

2

13}; Australian Autoimmune Encephalitis Consortium

Affiliations

¹ Department of Neuroscience, Monash University, Melbourne, Australia.
² Department of Neurology, Alfred Health, Melbourne, Australia.
³ Department of Radiology, Alfred Health, Melbourne, Australia.
⁴ Department of Radiology, Monash Health, Melbourne, Australia.
⁵ Department of Neurology, Princess Alexandra Hospital, Australia.
⁶ School of Medicine, The University of Queensland, Australia.
⁷ Department of Medicine, St Vincent's Hospital, University of Melbourne, Australia.
⁸ Department of Neurology, Austin Health, Melbourne, Australia.
⁹ Department of Neuroscience, University Hospital Geelong, Geelong, Australia.
¹⁰ Department of Neurosciences, Eastern Health, Melbourne, Australia.
¹¹ Department of Pathology, St Vincent's Hospital, Melbourne, Australia.
¹² Department of Neurology, Royal Hobart Hospital, Australia.
¹³ Department of Neurology, Royal Melbourne Hospital, Australia.
¹⁴ Division of Immunology, Pathology Queensland Central Laboratory, Herston, Australia.
¹⁵ Department of Neurology, Peninsula Health, Australia.
¹⁶ CORe, Department of Medicine, The University of Melbourne, Australia.
¹⁷ Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Australia.
¹⁸ Department of Neuroscience, Monash Health, Melbourne, Australia.
¹⁹ Department of Neurology and Concord Clinical School, Concord Hospital, Australia.
²⁰ Translational Neuroimmunology Group, Kids Neuroscience Centre and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Australia.
²¹ Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Australia.
²² Melbourne School of Psychological Sciences, University of Melbourne, Australia; and.
²³ Brain and Mind Centre, University of Sydney, Australia.

PMID: 40446185
PMCID: PMC12153942
DOI: 10.1212/NXI.0000000000200395

Multicenter Study

Rituximab Use for Relapse Prevention in Anti-NMDAR Antibody-Mediated Encephalitis: A Multicenter Cohort Study

Nabil Seery et al. Neurol Neuroimmunol Neuroinflamm. 2025 Jul.

. 2025 Jul;12(4):e200395.

doi: 10.1212/NXI.0000000000200395. Epub 2025 May 30.

Authors

Affiliations

¹ Department of Neuroscience, Monash University, Melbourne, Australia.
² Department of Neurology, Alfred Health, Melbourne, Australia.
³ Department of Radiology, Alfred Health, Melbourne, Australia.
⁴ Department of Radiology, Monash Health, Melbourne, Australia.
⁵ Department of Neurology, Princess Alexandra Hospital, Australia.
⁶ School of Medicine, The University of Queensland, Australia.
⁷ Department of Medicine, St Vincent's Hospital, University of Melbourne, Australia.
⁸ Department of Neurology, Austin Health, Melbourne, Australia.
⁹ Department of Neuroscience, University Hospital Geelong, Geelong, Australia.
¹⁰ Department of Neurosciences, Eastern Health, Melbourne, Australia.
¹¹ Department of Pathology, St Vincent's Hospital, Melbourne, Australia.
¹² Department of Neurology, Royal Hobart Hospital, Australia.
¹³ Department of Neurology, Royal Melbourne Hospital, Australia.
¹⁴ Division of Immunology, Pathology Queensland Central Laboratory, Herston, Australia.
¹⁵ Department of Neurology, Peninsula Health, Australia.
¹⁶ CORe, Department of Medicine, The University of Melbourne, Australia.
¹⁷ Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Australia.
¹⁸ Department of Neuroscience, Monash Health, Melbourne, Australia.
¹⁹ Department of Neurology and Concord Clinical School, Concord Hospital, Australia.
²⁰ Translational Neuroimmunology Group, Kids Neuroscience Centre and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Australia.
²¹ Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Australia.
²² Melbourne School of Psychological Sciences, University of Melbourne, Australia; and.
²³ Brain and Mind Centre, University of Sydney, Australia.

PMID: 40446185
PMCID: PMC12153942
DOI: 10.1212/NXI.0000000000200395

Abstract

Background and objectives: Rituximab is an anti-CD20 monoclonal antibody used in patients with anti-NMDAR antibody (Ab)-mediated encephalitis as both an acute escalation therapy and a longer term relapse risk-reduction treatment. The potential long-term benefit of a single course administered during the acute disease phase on future relapse risk is uncertain. Moreover, the optimal dosing duration to reduce relapse risk is unknown. The aim of this study was to evaluate the effect of a single course of rituximab on relapse incidence. We also studied the duration of effect of a course of rituximab in adult patients with anti-NMDAR Ab-mediated encephalitis.

Methods: We recruited 67 patients with anti-NMDAR Ab-mediated encephalitis from 10 Australian hospitals. Rituximab exposure was quantified as a time-varying covariate in Cox proportional hazard models.

Results: A single course of rituximab was associated with longer time to first relapse (hazard ratio [HR] 0.11, 95% CI 0.02-0.70, p = 0.02). For patients in whom redosing is considered, rituximab was associated with longer time to first relapse at 6 months after the last infusion, after adjusting for concurrent immunotherapies and the presence of ovarian teratoma at disease onset (HR 0.05, 95% CI 0.00-0.48, p = 0.005). The treatment effect did not persist out to 12 months after a given course (HR 0.60, 95% CI 0.15-2.44, p = 0.47).

Discussion: A single course of rituximab reduces the risk of relapse of anti-NMDAR antibody-mediated encephalitis. In select patients for whom redosing of rituximab is considered, administration at 6 months delays relapses.

Classification of evidence: This study provides Class IV evidence that rituximab delays relapses in patients with anti-NMDAR antibody-mediated encephalitis.

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Conflict of interest statement

S. Blum is and has been involved in clinical trials sponsored by Roche, Novartis, Sanofi-Genzyme, CSL, Clene Nanomedicine, Biogen, and Merck; and his institution has received honoraria for advisory boards and speaking honoraria from Biogen, Merck, Roche, and Novartis. H. Butzkueven is an employee of Monash University and has accepted travel compensation from Merck; his institution receives honoraria for talks, steering committee activities, and research grants from Roche, Merck, Biogen, Novartis, and UCB Pharma, Medical Research Future Fund Australia, National Health and Medical Research Council (NHMRC) Australia, Trish MS Foundation, MS Australia, and the Pennycook Foundation; he also receives personal compensation for steering group activities for the Brain Health Initiative from Oxford Health Policy Forum, and is funded by an NHMRC Australia Investigator Grant. K. Buzzard is a principal investigator in clinical trials for Novartis, Merck, Roche, and Biogen; has received speaker honoraria and/or travel grants from Sanofi Genzyme, Roche, Alexion, Merck, Biogen, Novartis, and Teva; and has been on advisory boards for Merck, Biogen, and UCB. T. Hardy has received honoraria for talks, advisory boards, or support for scientific meetings from Bayer-Schering, Novartis, Biogen Idec, Merck, Teva, Merck, Alexion, Bristol Myers Squibb, and Sanofi-Genzyme; has been the principal investigator on phase IV trials in MS funded by Novartis and Sanofi Genzyme; is co-editor of Advances in Clinical Neuroscience and Rehabilitation; and serves on the editorial boards of Journal of Neuroimmunology and Frontiers in Neurology. T. Kalincik served on scientific advisory boards for MS International Federation and World Health Organisation, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck, and Biogen; serves on the steering committee for Brain Atrophy Initiative by Sanofi Genzyme; received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL, and Merck; and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck. R. Macdonell or his institution has received remuneration for his speaking engagements, advisory board memberships, research, and travel from Biogen, Merck, Sanofi-Genzyme, Bayer, Roche, Teva, Novartis, CSL, BMS, MedDay, and NHMRC. L. McLaughlin has received educational event support from Roche, Biogen, and Merck. M. Monif has served on the advisory boards of Merck and Novartis; has received speaker honoraria from Merck, Biogen, and Novartis; and her institution receives funding from Merck, the Australian National Health Medical Research Council, and MS Research Australia. C. Nesbitt has received speaker honoraria and or educational travel support from Merck, Biogen, and Roche. S. Ramanathan has received research funding from the NHMRC (Australia), the Petre Foundation, the Brain Foundation, the Royal Australasian College of Physicians, and the University of Sydney; is supported by an NHMRC Investigator Grant (GNT2008339); serves as a consultant on an advisory board for UCB and Limbic Neurology; has been an invited speaker for educational/research sessions coordinated by Biogen, Alexion, Novartis, Excemed, and Limbic Neurology; and is on the medical advisory boards (non-remunerated positions) of the MOG Project and the Sumaira Foundation. S. Reddel has received funding over the last 5 years that includes but is not limited to travel support, honoraria, trial payments, research, and clinical support to the neurology department or academic projects of which the author is a member from bodies and charities: NHMRC, MRFF, NBA, Myasthenia Alliance Australia, and the Beeren Foundation; and from pharmaceutical/biological companies: Alexion, Biogen, CSL, Genzyme, Grifols, Merck, Novartis, Roche, Sandoz, Sanofi, and UCB. Additional interests and potential conflicts of interest include the following: cofounder/shareholder of RxPx Health, National IVIG Governance Advisory Council and Specialist Working Group Australia (Neurology) (paid), Australian Medical Services Advisory Committee ad hoc sub-committee on IVIG (paid), Australian Technical Advisory Group on Immunisation Varicella Zoster working party (unpaid); public salary as a staff specialist neurologist from Concord Hospital Sydney Local Health District (paid); rivate billings from patients and Medicare Australia reimbursement as a private practice neurologist (paid); medical advisor (unpaid) to various patient and advocacy groups. N. Seery has received conference fee sponsorship from Roche. T. Tan has received speaker honoraria from Eisai and travel support from Biogen. R. Wesselingh has nothing to declare. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.

Figures

**Figure 1. Schematic of Hypothetical Patients Evaluated Using Rituximab Treatment-Effect Models**
(A) Single-course rituximab model; (B) 6-month effect model; (C) 12-month effect model.

**Figure 2. Swimmer Plot Demonstrating Temporal Relation of Second-Line and Maintenance Immunotherapies to Relapses**
(A) Rituximab dosing: 2 induction doses of 1 g over a fortnightly period and weekly body surface area dosing up to 4 weeks treated as a single course and represented by a single symbol; cyclophosphamide dosing: 750 mg/m² or 15 mg/kg dosing per treatment, with reductions in dose as necessary; bortezomib dosing: each cycle represented by a cycle of subcutaneous dose of 1.3 mg/m² on days 1, 4, 8, and 11 of a 21-day cycle. (B) One patient excluded because of missing data for immunotherapy administered overseas. Abbreviations: IVIg = IV immunoglobulin; AZA = azathioprine; MMF = mycophenolate mofetil; MTX = methotrexate.

See this image and copyright information in PMC

References

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Rituximab Use for Relapse Prevention in Anti-NMDAR Antibody-Mediated Encephalitis: A Multicenter Cohort Study

Affiliations

Rituximab Use for Relapse Prevention in Anti-NMDAR Antibody-Mediated Encephalitis: A Multicenter Cohort Study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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LinkOut - more resources

Full Text Sources