What are the most effective treatments for NMDAR-antibody encephalitis?

September 21, 2021

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

This paper results from the hard work, dedication, and collaboration between the International NMDAR-antibody Encephalitis Consensus Group and other experts in the field, led by Dr. Margherita Nosadini, Dr. Michael Eyre, and Dr. Ming Lim. The paper aims to answer what treatments are the most effective for NMDAR-antibody encephalitis (NMDARE). And to answer this question, the authors performed a meta-analysis of 1,550 patients with NMDARE. 

Overall, immunotherapy has been shown to improve outcomes and reduce relapses in NMDAR-antibody encephalitis (NMDARE). However, it remains unclear if a specific treatment or treatment combination is superior in doing so. The authors mapped the use and safety of immunotherapy, identified early predictors of poor functional outcome and relapse, and looked to see if changes in immunotherapy use and outcome were seen over the 14 years since NMDARE was first reported.

Key findings

– Factors associated with good functional outcomes were adolescent age and first-line treatment with either plasmapheresis alone, corticosteroids with IVIG, or corticosteroids with IVIG and plasmapheresis. 

– Factors associated with poor functional outcome were infant or older adult age, ICU admission, EEG extreme delta brush pattern, lack of immunotherapy ≤30 days of onset, and maintenance IVIG treatment for ≥six months. 

– Relapsing disease was associated with adolescent age, and non-relapsing disease was associated with rituximab use or maintenance IVIG for ≥six months. 

Infants (<2 years) and older adults (≥65 years) suffered the worst outcomes of NMDARE, with 3.6- and 3.8-times increased odds of poor outcome respectively, while adolescents (12-19 years) had 2.6 times increased odds of a good outcome, compared to those aged 20-65 years. These outcomes may be related to differences in synaptic NMDAR composition in both the developing and aging brains. 

It was determined that plasmapheresis alone or first-line treatment options used in combination were effective in NMDARE providing support for a pragmatic approach to selecting first-line therapies guided by side-effect profile and patient acceptability.

Lack of immunotherapy within 30 days of disease onset (occurring in 49.9% of the total literature review cohort) was associated with increased odds of poor outcome. Rituximab was associated with a monophasic course, with 5.9 times reduced odds of relapse after ≥24 months follow-up. The authors’ analysis also showed that patients with earlier initiation of second-line therapy had 7.1 times reduced odds of poor outcome than those with later initiation, despite similar severity at the height of the disease. In their analysis of changes in immunotherapy use over time, the key finding was an increase in the use of rituximab concurrent with a generally falling relapse rate. However, the functional outcome did not improve over time. 

This comprehensive study emphasizes the importance of early immunotherapy and timely escalation to second-line treatments, mainly with rituximab. It also shows that clinical factors that often influence functional outcomes do not affect relapsing disease biology. 

AE Alliance wants to thank Dr. Lim, Dr. Nosadini, and Dr. Eyre, and other collaborators for this important and insightful work. Not only will this paper be of great use to how clinicians treat NMDARE today, but it will also prompt further research. 

Read the full article here