Abstract Details

Title Clinical and Biological Predictors of Quality of Life in CASPR2-antibody Encephalitis

Topic Autoimmune Neurology

Presentation(s) P8 - Poster Session 8 (11:45 AM-12:45 PM)

Poster/Presentation
Number 1-002

Objective

To assess the clinical and biological features that predict quality of life outcomes after immunotherapy in CASPR2-antibody disease.

Background

CASPR2-antibody disease is an autoantibody-mediated neurological disease which may present as limbic encephalitis, Morvan’s Syndrome or isolated peripheral nerve hyperexcitability (PNH). To date, there have been conflicting reports about the factors associated with worse clinical outcomes. Neuropathic pain (NeuP) and fatigue are important drivers of disability and worsened quality of life (QoL), but their degree of response to immunotherapy is contested.

Design/Methods

75 patients with CASPR2-antibody seropositivity and a relevant clinical syndrome were included. Outcome measures including symptom persistence, EuroQoL-5D-5L QoL scores, modified Rankin scale (mRS) and pain measures were collected retrospectively over a 6-year study period. Patient sera across multiple time points were interrogated by live cell-based assay and flow cytometry-based immunoglobulin G subclass assays. Clinical and biological predictors were assessed with multiple logistic regression and univariate analysis.

Results

Despite most symptoms responding to immunotherapy in the first 6-12 months, NeuP and fatigue emerged as the most prominent and persistent symptoms, associated with a worse clinical trajectory of recovery and predicting worse disability, QoL and risk of relapse.

While other QoL domains improved, pain scores did not change over time. IgG1 levels were higher in the LE cohort (p<0.001) and NeuP was associated with lower IgG1 levels in the early phase (<12 months) of the disease (p=0.01). The presence of the human leukocyte antigen (HLA) DRB1:11*01 allele was associated with less NeuP (p=0.001) and better QoL (p=0.01) at 2 years.

Conclusions

NeuP and fatigue are prominent residual features of CASPR2-antibody disease which do not respond to immunotherapy. IgG subclass analysis suggests IgG1 may have a more limbic predilection, versus a more peripheral, IgG4-mediated effect in causing NeuP. HLA genotyping may be a useful biomarker to predict clinical outcomes.

Authors/Disclosures
Bryan Ceronie, MBBS PRESENTER	No disclosure on file
Ikram Ayoub, PhD	Dr. Ayoub has nothing to disclose.
Christine Strippel, MD	Dr. Strippel has nothing to disclose.
Barry A. Michael, MD	Dr. Michael has received personal compensation for serving as an employee of Eisai.
Christopher E. Uy, MD (Vancouver Coastal Health)	Dr. Uy has received personal compensation in the range of $500-$4,999 for serving as a IVIG for CNS Disease Task Force Member with Provincial Blood Coordinating Office (British Columbia).
John Dawes, PhD	Dr. Dawes has nothing to disclose.
David Bennett, MD, PhD	Prof. Bennett has a non-compensated relationship as a Consultant with AditumBio that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with AstraZeneca that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with Biogen that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with Biointervene that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with Combigene that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with LatigoBio that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with GSK that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with Ionis that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with Lexicon therapeutics that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with Neuvati that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with Novo Ventures 2023 that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consutlant with Olipass that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with Orion that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with Replay that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with SC Health Managers that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with Third Rock ventures that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a Consultant with Vida Ventures that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a received research funding with Lily that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a received research funding with Astra Zeneca that is relevant to AAN interests or activities. Prof. Bennett has a non-compensated relationship as a received an industrial partnership grant from AZ & the BBSRC with Astra Zeneca that is relevant to AAN interests or activities.
Sophie Binks, MD, MBBS, PhD	The institution of Dr. Binks has received research support from Wellcome Trust. The institution of Dr. Binks has received research support from PetSavers. The institution of Dr. Binks has received research support from PetPlan. The institution of Dr. Binks has received research support from NIHR. The institution of Dr. Binks has received research support from Morris Animal Foundation. Dr. Binks has received personal compensation in the range of $0-$499 for serving as a Speaker with ECTRIMS. Dr. Binks has received personal compensation in the range of $0-$499 for serving as a Speaker with Vetmeduni Wien. Dr. Binks has received personal compensation in the range of $0-$499 for serving as a Speaker with ANA. Dr. Binks has a non-compensated relationship as a Speaker with Encephalitis Society UK that is relevant to AAN interests or activities. Dr. Binks has a non-compensated relationship as a Scientific Panel Member with Encephalitis International that is relevant to AAN interests or activities. Dr. Binks has a non-compensated relationship as a Editorial Fellow with JAMA Neurology that is relevant to AAN interests or activities.
Adam Handel (University of Oxford)	The institution of Adam Handel has received research support from Medical Research Council (UK). The institution of Adam Handel has received research support from UCB-Pharma. The institution of Adam Handel has received research support from MyAware.
Sarosh R. Irani, MD, PhD, FRCP, FEAN (Mayo Clinic)	Dr. Irani has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for AZ, Roche, Cerebral therapeutics, Biogen, Amgen, Argenex, Clarivate, IQVIA, BioHaven therapeutics.. Dr. Irani has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Brain. Dr. Irani has received intellectual property interests from a discovery or technology relating to health care. Dr. Irani has received intellectual property interests from a discovery or technology relating to health care.

��ɫ��

��ɫ��