NEOSII: Predicting Functional Outcome and Response to Therapy of Anti-NMDAR Encephalitis at Diagnosis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Dutch National anti-NMDAR Encephalitis Cohort Dutch National anti-NMDAR Encephalitis Cohort |
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| German anti-NMDAR Encephalitis Cohort (GENERATE) German anti-NMDAR Encephalitis Cohort (GENERATE) |
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| Spanish anti-NMDAR Encephalitis Cohort Spanish anti-NMDAR Encephalitis Cohort |
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| French anti-NMDAR Encephalitis Cohort French anti-NMDAR Encephalitis Cohort |
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| Japanese anti-NMDAR Encephalitis Cohort Japanese anti-NMDAR Encephalitis Cohort |
Outcome Measures
Primary Outcome Measures
- Functional status one year after diagnosis, on the modified Rankin Scale. [One year after diagnosis]
The score on the modified Rankin Scale will be applied as the original ordinal scale as well as dichotomized, where scores 0-2 represent "independent functioning" (without or with symptoms) and scores 3-6 increasing levels of depencency
Secondary Outcome Measures
- Response to first-line immunotherapy [Two weeks after administration of first-line immunotherapy]
One point improvement (one point lower than at diagnosis) on the modified Rankin Scale (ranging from 0 - no symptoms - to 6 - deceased - as the most severe category) within two weeks from therapy commencement.
- Return to school or work [Throughout follow-up time after diagnosis (different per patient, depending on date of diagnosis). Average 3 years (min 0 - max 22 years)]
Time-to-event analysis on the ability to return to school or work during follow-up, including timing of resumption of work after diagnosis.
- Relapse rate [Throughout follow-up time after diagnosis (different per patient, depending on date of diagnosis). Average 3 years (min 0 - max 22 years)]
Time-to-event analysis on relapses during total available follow-up time, including time of relapse after diagnosis.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Diagnosed with anti-NMDAR encephalitis (according to the Graus criteria)
Exclusion Criteria:
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Preceding Herpes Simplex encephalitis
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Premorbid dependency (modified Rankin Scale > 2)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Erasmus Medical Center | Rotterdam | Netherlands |
Sponsors and Collaborators
- Erasmus Medical Center
Investigators
- Principal Investigator: Maarten J. Titulaer, Assoc. Porf., Erasmus Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NEOSII