Cancer drug repurposed to calm brain inflammation in autoimmune disease

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Aged ≥18 years, male or female. * Confirmed diagnosis of antibody-positive autoimmune encephalitis (AE) or autoimmune cerebellitis (ACA). * Refractory AE/ACA defined as antibody-positive disease meeting all of the following: * Modified Rankin Scale (mRS) score \>3 (stable for at least 24 hours) at baseline. * Received first-line acute therapy more than 6 weeks prior to baseline visit, defined as at least 3 days of intravenous methylprednisolone (≥500 mg/day) or equivalent oral corticosteroids, and/or at least 3 days of IVIG and/or plasma exchange (PE), or any combination thereof. * Received additional immunotherapy beyond the first acute course, meeting the following: 1. For rituximab: treatment initiated at least 2 months prior to screening, last dose at least 4 weeks prior to baseline, and no improvement in mRS score for 2 months before baseline. 2. For other immunosuppressive therapies (IST; e.g., mycophenolate mofetil, cyclophosphamide, azathioprine): treatment for at least 2 months prior to screening, stable dose for at least 4 weeks prior to baseline, and no improvement in mRS score for 4 weeks before baseline. 3. For oral corticosteroids: stable dose \>20 mg/day prednisone equivalent, no dose increase for 4 weeks prior to baseline, and no improvement in mRS score for 4 weeks before baseline. 4. For repeated first-line therapy courses: completed at least 2 weeks prior to baseline visit. * For patients on oral corticosteroids: stable dose ≥20 mg/day prednisone equivalent, no dose increase for 4 weeks prior to enrollment, and no improvement in mRS score for 4 weeks before enrollment. * For patients on rituximab: treatment initiated at least 2 months prior to enrollment, last dose at least 4 weeks prior to enrollment, and no improvement in mRS score for 4 weeks before enrollment. * For patients on other IST (e.g., azathioprine, mycophenolate mofetil): treatment for at least 2 months prior to enrollment, stable dose for at least 4 weeks prior to enrollment, and no improvement in mRS score for 4 weeks before enrollment. * For patients on repeated first-line therapy courses: completed at least 2 weeks prior to enrollment. * Patient or legally authorized representative provides written informed consent. * For females of childbearing potential: agreement to abstain from heterosexual intercourse or use adequate contraception during treatment and for at least 3 months after the last dose. Post-menopausal females (≥12 consecutive months of amenorrhea without other cause) or those permanently sterilized by surgery (e.g., bilateral oophorectomy, hysterectomy) are not considered of childbearing potential. Acceptable contraceptive methods include bilateral tubal ligation, male sterilization, hormonal contraceptives, hormonal IUDs, copper IUDs, male/female condoms with spermicide, and contraceptive diaphragms/caps with spermicide. Periodic abstinence and withdrawal are not considered adequate. Diagnostic Criteria for Antibody-Positive Autoimmune Encephalitis (AE): A. Clinical presentation: Acute or subacute onset (\<3 months) with ≥1 neuropsychiatric symptom: 1. Limbic encephalitis: memory impairment, seizures, psychiatric symptoms. 2. Encephalopathy syndrome: diffuse or multifocal brain dysfunction. 3. CSF pleocytosis (\>5×10⁶/L), lymphocytic inflammation, or oligoclonal bands. B. Investigations: ≥1 of the following or associated tumors: 1. CSF abnormalities as above. 2. Neuroimaging/EEG: MRI T2/FLAIR hyperintensity in limbic system or other regions (excluding non-specific white matter changes/stroke); PET hypermetabolism in limbic system or multifocal cortex/basal ganglia; EEG with focal epileptiform discharges or diffuse/multifocal slowing. 3. Specific tumors associated with AE. C. Confirmatory test: Positive anti-neuronal antibodies. D. Other causes excluded. All criteria A-D must be met. Diagnostic Criteria for Autoimmune Cerebellitis (ACA): 1. Acute or subacute onset with predominant cerebellar syndrome. 2. No significant cerebellar/brainstem atrophy on brain MRI within 3 months of onset. 3. Meets either 3.1 or 3.2: 3.1 Positive anti-cerebellar antibodies in serum and/or CSF detected by cell-based assay (CBA). 3.2 At least two of the following: personal or first-degree family history of autoimmune disease; CSF pleocytosis (\>5×10⁶/L) or oligoclonal bands; characteristic immunofluorescence pattern of anti-Purkinje cell antibodies on tissue-based assay (TBA); presence of systemic autoimmune disease-related antibodies. 4. Other causes excluded. Exclusion Criteria: * Systemic or central nervous system tumors (e.g., gliomatosis cerebri), history of cancer (excluding ovarian/extra-ovarian teratoma, skin squamous cell carcinoma, or basal cell carcinoma with documented cure ≥3 months prior to enrollment); hereditary diseases (e.g., mitochondrial encephalopathy); neurodegenerative diseases (e.g., Lewy body dementia); prior epilepsy with ongoing seizures; severe traumatic brain injury; metabolic/toxic encephalopathy (e.g., Wernicke encephalopathy). * Infectious diseases (e.g., viral encephalitis); active or uncontrolled infection requiring systemic treatment within 1 week prior to screening; history of severe recurrent or chronic infections, especially respiratory infections. * Positive hepatitis B surface antigen/核心 antigen and/or positive hepatitis C PCR at screening. * Active tuberculosis at screening. * Diseases requiring long-term corticosteroid or immunosuppressive therapy. * Known history of primary immunodeficiency (congenital or acquired) or conditions predisposing to infection (e.g., HIV infection, splenectomy). * History of solid organ or hematopoietic stem cell transplantation within 3 months prior to screening. * Live or attenuated vaccine within 3 weeks prior to enrollment (inactivated vaccines are allowed); BCG vaccine within 1 year prior to enrollment. * Congenital heart disease, acute myocardial infarction within 6 months prior to screening, severe arrhythmias (e.g., polymorphic ventricular tachycardia), moderate to large pericardial effusion, severe myocarditis, hemodynamic instability requiring vasopressors, left ventricular ejection fraction (LVEF) ≤55%, or significant ECG abnormalities. * Any of the following laboratory abnormalities: * Absolute lymphocyte count (ALC) ≤0.5×10⁹/L * Absolute neutrophil count (ANC) ≤0.5×10⁹/L * Immunoglobulin G (IgG) ≤5.0 g/L * CD4 T-cell count \<300 cells/µL * Hemoglobin ≤80 g/L * Platelet count ≤75×10⁹/L * Estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73m² * AST/ALT ≥3× upper limit of normal (ULN); total bilirubin ≥2×ULN * Pregnant or breastfeeding females, or those planning pregnancy during the trial. * Incomplete medical records or refusal to participate in the registry. * Known allergy or hypersensitivity to any component of the study drug or to any biologic therapy.