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

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

Jennifer H Yang  1 , Emilie N Liu  2 , Linda Nguyen  2 , Anastasie Dunn-Pirio  2 , Jennifer S Graves  2
Affiliations

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

Jennifer H Yang et al. Neurology. .

Erratum in

  • Corrections to Received Date Information.
    [No authors listed] [No authors listed] Neurology. 2024 Jul 9;103(1):e209596. doi: 10.1212/WNL.0000000000209596. Epub 2024 Jun 3. Neurology. 2024. PMID: 38830175 Free PMC article. No abstract available.

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.

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Conflict of interest statement

J.H. Yang, E. Liu, and L. Nguyen report no disclosures relevant to the manuscript; A. Dunn-Pirio reports no disclosures relevant to the manuscript; J.S. Graves has received grant or clinical trial funding from the NMSS, UCSD, Octave, Biogen, EMD-Serono, and ABM. She serves on a steering committee for a clinical trial with Novartis and served on advisory boards for TG therapeutics, Genentech, and Bayer unrelated to the current work. Go to Neurology.org/N for full disclosures.

Figures

Figure 1
Figure 1. Study Population
AchR = acetylcholine receptor; AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; ANNA2 (Ri) = antineuronal nuclear autoantibody type 2; CASPR2 = contactin-associated protein-like 2; CRMP5 = CV2/collapsin response mediator protein; GABA = gamma-aminobutyric acid; GAD65 = glutamic acid decarboxylase 65; GFAP = glial fibrillary acidic protein; Hu/ANNA1 = antineuronal nuclear autoantibody type 1; LGI1 = leucine-rich glioma-inactivated 1; TPO = thyroid peroxidase; VGKC = voltage-gated potassium channel; Yo = Purkinje cell cytoplasmic antibody type 1. aTwo patients had more than one autoantibody.
Figure 2
Figure 2. Survival Analysis of Relapse Rates for Combined Pediatric and Adult Cohorts
Kaplan-Meier curves for time to first relapse (A) and overall relapse rate over the total follow-up period (B) in both pediatric and adult patients.
See this image and copyright information in PMC

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Supplementary concepts