Medium-term Effects of Treatments in Autoimmune Encephalitis (META)

Medium-term Effects of Treatments in Autoimmune Encephalitis (META): a Real-life, Observational Prospective Study

Autoimmune encephalitides are severe neurological disorders requiring urgent treatment, even though there is no standard guideline by lack of empirical evidence. Commonly used treatments are divided into so-called first-line (steroids, intravenous immunoglobulins, plasma exchanges) and second-line (rituximab, cyclophosphamide, tocilizumab, others), and may be used in association or sequentially. There is no standard practice, and initial treatment protocol may consist in first-line alone, first-line with rituximab, or first-line with dual immunosuppression (rituximab and cyclophosphamide). Absence of clear response to initial treatment in the first 4 to 6 weeks may indicate undertreatment and is generally followed by treatment escalation, mostly to dual immunosuppression. However, as the frequency of non-responders to initial treatment is unknown, it is still unclear whether dual immunosuppression should be offered to all patients from inception.

Study Overview

• Status: Recruiting
• Conditions: CASPR2-Antibody; NMDAR Autoimmune Encephalitis; LGI1 Antibody Associated Encephalitis; GFAP; IgLON5; GAD65
• Intervention / Treatment: Other: We aim to assess the clinical response to the treatment initiation protocols most commonly used in autoimmune encephalitis (first-line, first-line with rituximab, dual immunosuppression).

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Bastien Pr JOUBERT; Phone Number: 04 78 86 17 89; Email: bastien.joubert@chu-lyon.fr
• Study Contact Backup: Name: Géraldine PICARD; Phone Number: 04.72.35.58.42; Email: geraldine.picard@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69677
    • Recruiting
    • Hospices Civil de Lyon
    • Contact: Bastien JOUBERT, Professor; Phone Number: 04 78 86 17 89; Email: bastien.joubert@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All Patients with autoimmune encephalitis defined anti-GAD NMDAR, LGI1, CASPR2, IgLON5 or GFAP and untreated within the previous 30 days

Description

Inclusion Criteria:

• Adult or child patient with encephalitis defined as anti-GAD, NMDAR, LGI1, CASPR2, IgLON5 or GFAP
• Untreated or with a decision to treat within the previous 30 days.

Exclusion Criteria:

- Refusal by the referring doctor to participate or refusal by the patient mentioned in the objection to the use of his/her clinical data.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
group 1 : Patients with NMDAR encephalitis; Patients with untreated anti-NMDAR encephalitis or with a decision to treat within the previous 30 days	Other: We aim to assess the clinical response to the treatment initiation protocols most commonly used in autoimmune encephalitis (first-line, first-line with rituximab, dual immunosuppression).; The patients will be identified via the French Nationwide Multidisciplinary Team Meetings for Autoimmune encephalitis, which are conducted on a bi-monthly basis. All patients with newly diagnosed NMDAR, LGI1, CASPR2, IgLON5, GFAP or GAD65 encephalitis and treated for less than 8 weeks will be included. Treatment protocols at the initiation of therapy will be stratified into: 1) first-line only; 2) rituximab without cyclophosphamide; 3) rituximab combined with cyclophosphamide; 4) others. The referral clinicians will be contacted by email and the data will be collected using standardized questionnaires, which will be sent at baseline (visit 1, V1) and 4 months after the initiation of therapy (visit 2, V2). The questionnaires will be structured into 7 sections: 1 Demographics; 2 Symptoms; 3 Cognitive screening tests (MMSE, MoCA, and/or others); 4 Level of dependence (ADL, I-ADL, mRS, CASE) and impact on social life; 5 Diagnostic tests (brain MRI, brain PET, CSF, and EEG findings)
group 2 : Patients with GAD encephalitis; Patients with untreated anti-GAD encephalitis or with a decision to treat within the previous 30 days	Other: We aim to assess the clinical response to the treatment initiation protocols most commonly used in autoimmune encephalitis (first-line, first-line with rituximab, dual immunosuppression).; The patients will be identified via the French Nationwide Multidisciplinary Team Meetings for Autoimmune encephalitis, which are conducted on a bi-monthly basis. All patients with newly diagnosed NMDAR, LGI1, CASPR2, IgLON5, GFAP or GAD65 encephalitis and treated for less than 8 weeks will be included. Treatment protocols at the initiation of therapy will be stratified into: 1) first-line only; 2) rituximab without cyclophosphamide; 3) rituximab combined with cyclophosphamide; 4) others. The referral clinicians will be contacted by email and the data will be collected using standardized questionnaires, which will be sent at baseline (visit 1, V1) and 4 months after the initiation of therapy (visit 2, V2). The questionnaires will be structured into 7 sections: 1 Demographics; 2 Symptoms; 3 Cognitive screening tests (MMSE, MoCA, and/or others); 4 Level of dependence (ADL, I-ADL, mRS, CASE) and impact on social life; 5 Diagnostic tests (brain MRI, brain PET, CSF, and EEG findings)
group 3 : Patients with LGI1 encephalitis; Patients with untreated anti-LGI1 encephalitis or with a decision to treat within the previous 30 days	Other: We aim to assess the clinical response to the treatment initiation protocols most commonly used in autoimmune encephalitis (first-line, first-line with rituximab, dual immunosuppression).; The patients will be identified via the French Nationwide Multidisciplinary Team Meetings for Autoimmune encephalitis, which are conducted on a bi-monthly basis. All patients with newly diagnosed NMDAR, LGI1, CASPR2, IgLON5, GFAP or GAD65 encephalitis and treated for less than 8 weeks will be included. Treatment protocols at the initiation of therapy will be stratified into: 1) first-line only; 2) rituximab without cyclophosphamide; 3) rituximab combined with cyclophosphamide; 4) others. The referral clinicians will be contacted by email and the data will be collected using standardized questionnaires, which will be sent at baseline (visit 1, V1) and 4 months after the initiation of therapy (visit 2, V2). The questionnaires will be structured into 7 sections: 1 Demographics; 2 Symptoms; 3 Cognitive screening tests (MMSE, MoCA, and/or others); 4 Level of dependence (ADL, I-ADL, mRS, CASE) and impact on social life; 5 Diagnostic tests (brain MRI, brain PET, CSF, and EEG findings)
group 4 : Patients with IgLON5 encephalitis; Patients with untreated anti-IgLON5 encephalitis or with a decision to treat within the previous 30 days	Other: We aim to assess the clinical response to the treatment initiation protocols most commonly used in autoimmune encephalitis (first-line, first-line with rituximab, dual immunosuppression).; The patients will be identified via the French Nationwide Multidisciplinary Team Meetings for Autoimmune encephalitis, which are conducted on a bi-monthly basis. All patients with newly diagnosed NMDAR, LGI1, CASPR2, IgLON5, GFAP or GAD65 encephalitis and treated for less than 8 weeks will be included. Treatment protocols at the initiation of therapy will be stratified into: 1) first-line only; 2) rituximab without cyclophosphamide; 3) rituximab combined with cyclophosphamide; 4) others. The referral clinicians will be contacted by email and the data will be collected using standardized questionnaires, which will be sent at baseline (visit 1, V1) and 4 months after the initiation of therapy (visit 2, V2). The questionnaires will be structured into 7 sections: 1 Demographics; 2 Symptoms; 3 Cognitive screening tests (MMSE, MoCA, and/or others); 4 Level of dependence (ADL, I-ADL, mRS, CASE) and impact on social life; 5 Diagnostic tests (brain MRI, brain PET, CSF, and EEG findings)
group 5 : Patients with GFAP encephalitis; Patients with untreated anti-GFAP encephalitis or with a decision to treat within the previous 30 days	Other: We aim to assess the clinical response to the treatment initiation protocols most commonly used in autoimmune encephalitis (first-line, first-line with rituximab, dual immunosuppression).; The patients will be identified via the French Nationwide Multidisciplinary Team Meetings for Autoimmune encephalitis, which are conducted on a bi-monthly basis. All patients with newly diagnosed NMDAR, LGI1, CASPR2, IgLON5, GFAP or GAD65 encephalitis and treated for less than 8 weeks will be included. Treatment protocols at the initiation of therapy will be stratified into: 1) first-line only; 2) rituximab without cyclophosphamide; 3) rituximab combined with cyclophosphamide; 4) others. The referral clinicians will be contacted by email and the data will be collected using standardized questionnaires, which will be sent at baseline (visit 1, V1) and 4 months after the initiation of therapy (visit 2, V2). The questionnaires will be structured into 7 sections: 1 Demographics; 2 Symptoms; 3 Cognitive screening tests (MMSE, MoCA, and/or others); 4 Level of dependence (ADL, I-ADL, mRS, CASE) and impact on social life; 5 Diagnostic tests (brain MRI, brain PET, CSF, and EEG findings)
group 6 : Patients with CASPR2 encephalitis; Patients with untreated anti-CASPR2 encephalitis or with a decision to treat within the previous 30 days	Other: We aim to assess the clinical response to the treatment initiation protocols most commonly used in autoimmune encephalitis (first-line, first-line with rituximab, dual immunosuppression).; The patients will be identified via the French Nationwide Multidisciplinary Team Meetings for Autoimmune encephalitis, which are conducted on a bi-monthly basis. All patients with newly diagnosed NMDAR, LGI1, CASPR2, IgLON5, GFAP or GAD65 encephalitis and treated for less than 8 weeks will be included. Treatment protocols at the initiation of therapy will be stratified into: 1) first-line only; 2) rituximab without cyclophosphamide; 3) rituximab combined with cyclophosphamide; 4) others. The referral clinicians will be contacted by email and the data will be collected using standardized questionnaires, which will be sent at baseline (visit 1, V1) and 4 months after the initiation of therapy (visit 2, V2). The questionnaires will be structured into 7 sections: 1 Demographics; 2 Symptoms; 3 Cognitive screening tests (MMSE, MoCA, and/or others); 4 Level of dependence (ADL, I-ADL, mRS, CASE) and impact on social life; 5 Diagnostic tests (brain MRI, brain PET, CSF, and EEG findings)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure of the initial treatment protocol	Failure of the initial treatment protocol, reflected by the decision to escalate treatment between V1 and V2. Treatment escalation is defined as the addition of one or more second-line treatments more than 30 days after the start of the initial treatment.	At baseline and 4 months after the initiation of therapy

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Actual): September 1, 2024
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: August 13, 2025
• First Submitted That Met QC Criteria: August 13, 2025
• First Posted (Actual): August 20, 2025

Study Record Updates

• Last Update Posted (Actual): August 20, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: autoimmune encephalitis; Paraneoplastic neurological disorder
• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Thyroid Diseases; Thyroiditis, Autoimmune; Thyroiditis; Encephalitis; Autoimmune Diseases of the Nervous System; Hashimoto Disease; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Rituximab
• Other Study ID Numbers: 24-5346

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No