Survival Analysis of Immunotherapy Effects on Relapse Rate in Pediatric and Adult Autoimmune Encephalitis

Jennifer H Yang; Emilie N Liu; Linda Nguyen; Anastasie Dunn-Pirio; Jennifer S Graves

doi:10.1212/WNL.0000000000207746

Survival Analysis of Immunotherapy Effects on Relapse Rate in Pediatric and Adult Autoimmune Encephalitis

Neurology. 2023 Nov 27;101(22):e2300-e2313. doi: 10.1212/WNL.0000000000207746.

Authors

Jennifer H Yang¹, Emilie N Liu², Linda Nguyen², Anastasie Dunn-Pirio², Jennifer S Graves²

Affiliations

¹ From the Department of Neurosciences (J.H.Y., L.N., A.D.-P., J.S.G.), University of California, San Diego; Rady Children's Hospital San Diego (J.H.Y., L.N., J.S.G.); and School of Medicine (E.N.L.), University of California, San Diego. jhy045@ucsd.edu.
² From the Department of Neurosciences (J.H.Y., L.N., A.D.-P., J.S.G.), University of California, San Diego; Rady Children's Hospital San Diego (J.H.Y., L.N., J.S.G.); and School of Medicine (E.N.L.), University of California, San Diego.

PMID: 37827848
PMCID: PMC10727225 (available on 2024-11-28)
DOI: 10.1212/WNL.0000000000207746

Abstract

Background and objectives: Prior observational studies for autoimmune encephalitis (AE) have mostly focused on outcomes after acute immunotherapies with better outcomes associated with earlier immunotherapy use. However, the impact of long-term immunotherapy and its association with clinical relapse is not well known.

Methods: We conducted a retrospective study of consecutive patients meeting published clinical criteria for AE evaluated at UC San Diego and Rady Children's Hospital from January 2007 to November 2021. Survival analysis and Cox multivariable regression models were used to evaluate relapse risk using rituximab exposure as a time-dependent variable. Pooled and age-stratified analyses were performed.

Results: A total of 204 pediatric and 380 adult participants were screened of which 30 pediatric and 75 adult participants were included. The most common antibody subtype in both cohorts was anti-NMDA receptor (76% in pediatric, 34% in adult). Relapses occurred in 31% of pediatric antibody-positive, 40% of adult antibody-positive, and 20% of adult antibody-negative cases. Times to first relapse (TTFR) were 10.6 ± 7.4 months (pediatric antibody-positive), 13.1 ± 24.5 months (adult antibody-positive), and 6.9 ± 3.8 months (adult antibody-negative). Rituximab was the most common second-line immunotherapy used. Combining pediatric and adult data, rituximab use was associated with a 71% lower hazard for time to first relapse (hazard ratio [HR] 0.29, 95% CI 0.09-0.85) and 51% lower hazard for recurring relapses (HR 0.49, 95% CI 0.9-1.26). The HR for TTFR with rituximab use in children was 0.30 (95% CI 0.05-1.69), 0.29 (95% CI 0.07-1.29) in adults, 0.32 in non-NMDA antibody-positive encephalitis (95% CI 0.07-1.39), and 0.42 (95% CI 0.07-2.67) for anti-NMDAR.

Discussion: Relapses are common in pediatric and adult patients with AE, although less frequently in anti-NMDARE. Using a rigorous survival model, we demonstrate a substantial benefit of rituximab use for reducing relapse rates in AE, especially for the adult population.

Classification of evidence: This study provides Class IV evidence that rituximab is associated with a lower hazard to relapse in patients with AE.

MeSH terms

Adult
Anti-N-Methyl-D-Aspartate Receptor Encephalitis* / drug therapy
Autoimmune Diseases of the Nervous System* / drug therapy
Child
Chronic Disease
Encephalitis* / drug therapy
Humans
Immunotherapy
Recurrence
Retrospective Studies
Rituximab / therapeutic use
Survival Analysis

Substances

Rituximab

Supplementary concepts

Hashimoto's encephalitis