Clinical trial NCT06023160: Predicting Functional Outcome and Response to Therapy of Anti-NMDAR Encephalitis at Diagnosis
Official title: Predicting Functional Outcome and Response to Therapy of Anti-NMDAR Encephalitis at Diagnosis: The NEOSII Score
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Anti-NMDA (N-Methyl D-Aspartate) Receptor Encephalitis
Keywords: Prognosis
Immunotherapy
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2023-09-05
Enrollment: 714
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Retrospective data of five (inter)national anti-NMDAR encephalitis cohorts.

Brief summary: The goal of this international cohort study is to develop a prediction model for long-term outcome and response to first-line immunotherapy of anti-NMDAR Encephalitis, already at the moment of diagnosis.

Detailed description: Anti-NMDARE is a severe, but treatable neurological condition, with considerable and variable long-term disability. The previously developed anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score predicts outcome a month into treatment. To predict outcome and response to immunotherapy at the time of diagnosis would be a serious improvement. This would timely identify patients in need for aggressive treatment and avoid harmful side-effects in those with good outcome. International data from five anti-NMDAR encephalitis cohorts will be combined to attain these goals.

The investigators strive to have less than 10% missing data on all variables and will impute data were needed. The datasets will then be split - with equal distributions of cohorts and good/poor outcome - to develop (70%) and validate (30%) the NEOS2 model. The primary outcome is functioning one year after diagnosis. A secondary analysis is targeted to predict the effect of first-line therapy. Potentially relevant predictive variables are identified with a univariable analysis on the original data, confirmed with backwards selection on the imputed datasets. After checking for multicollinearity and linearity of the variables, identified variables are added to a mixed effects logistic regression model on the original and imputed datasets, to identify the final set of predictive variables. To make the models opportune for daily medical practice, the investigators will assign points to (categories of) the included variables, based on the coefficients.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with anti-NMDAR encephalitis (according to the Graus criteria)

Exclusion Criteria:

* Preceding Herpes Simplex encephalitis
* Premorbid dependency (modified Rankin Scale \> 2)

Primary outcomes:
measure: Functional status one year after diagnosis, on the modified Rankin Scale.
timeFrame: One year after diagnosis
Secondary outcomes:
measure: Response to first-line immunotherapy
timeFrame: Two weeks after administration of first-line immunotherapy
measure: Return to school or work
timeFrame: Throughout follow-up time after diagnosis (different per patient, depending on date of diagnosis). Average 3 years (min 0 - max 22 years)
measure: Relapse rate
timeFrame: Throughout follow-up time after diagnosis (different per patient, depending on date of diagnosis). Average 3 years (min 0 - max 22 years)
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
Study officials:
affiliation: Erasmus Medical Center
name: Maarten J. Titulaer, Assoc. Porf.
role: PRINCIPAL_INVESTIGATOR
References: