CPI Combination Therapy for Autoimmune Encephalitis

Xuanwu Hospital, Beijing70 enrolled

Overview

Corticosteroids, intravenous immunoglobulin (IVIG), and plasma exchange (PE) are the first-line therapies for autoimmune encephalitis (AE) patients, but optimal first-line treatment strategy for different AE patients remains undetermined. The study is to compare the efficacy between pulse corticosteroid plus PE initially followed by IVIG (CPI therapy) and pulse corticosteroid plus IVIG followed by PE two weeks later (CIP therapy) in patients with severe antibody-associated autoimmune encephalitis (AE).

Patients with AE will be randomly divided into the CPI and CIP group according to the random table. All patients will receive tumour screening, symptomatic supportive treatment, and immunotherapy. The immunotherapy includes intravenous methylprednisolone (IVMP), intravenous immunoglobulin (IVIG; 0.4 g/kg/d for each course for 5 d), PE and immunosuppressants. Patients in the CPI group received IVMP and PE treatment without delay, followed by IVIG immediately after PE treatment. Patients in the CIP group were given IVMP and IVIG and IVMP immediately, followed by PE at least 2 weeks after IVIG treatment. The patients received long-term immunotherapy involving a combination of oral corticosteroids and immunosuppressants (such as mycophenolate mofetil at a dose of 1-2g/d) for 6-12 months if no contraindications. The primary outcome is the proportion of patients achieving functional improvement \[a decrease of at least 1 point in modified Rankin Scale (mRS) score\] at 3 months after immunotherapy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Autoimmune Encephalitis

Interventions

Plasma exchange (PE)PROCEDURE

PE is performed every other day using a multi-filtrate apheresis device (Fresenius, Bad Homburg, Germany), and 5 times in total for each course. The plasma removed during PE is replaced with an equal volume of substitution (half 5% albumin with normal saline and half plasma). The plasma volume to be replaced was estimated according to the following formula: plasma volume (L) = 7.5%×weight (kg)×(1-hematocrit)×1000ml. Heparin was added to the exchange circuit to prevent blood clotting. The exchange rate was monitored, recorded, and balanced to prevent cardiovascular instability. Blood pressure and other vital signs were closely monitored every 15 minutes throughout the exchange.

intravenous immunmoglobulin (IVIG), intravenous methylprednisolone (IVMP)DRUG

IVIG is given 0.4 g/kg/d for each course for 5 days. IVMP is 1,000 mg or 500 mg methylprednisolone for 3 or 5 days, and the dosage of glucocorticoid will gradually decrease.

Eligibility

Sex: ALLMin age: 14 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. 14-65 years old; 2. met all the three following diagnostic criteria of AE: (i) subacute onset (rapid progress of less than 3 months) of working memory deficits, altered mental status, or psychiatric symptoms; (ii) at least one of the followings: new focal CNS findings, seizures not explained by a previously known disease, cerebrospinal fluid (CSF) pleocytosis (white blood cell count 5 cells/mm3), magnetic resonance imaging (MRI) features suggestive of encephalitis, and (iii) reasonable exclusion of alternative causes; 3. the presence of antibody against neuronal surface antigen in serum or CSF indicating a positive diagnosis of AE using a cell-based assay; 4. critically ill with a modified Rankin scale (mRS) score of 4 to 5; 5. within 3 months of onset; 6. no immunotherapy previously. Exclusion criteria: 1. relative contraindications of TPE treatment: serious underlying diseases such as severe active hemorrhage, disseminated intravascular coagulation, severe hypotension or shock, unstable cardiac failure, cerebral herniation, severe infection or other endangered conditions; 2. allergic to immunoglobulin; 3. contraindications of glucocorticoid therapy: glucocorticoid allergy, active gastric or duodenal ulcer, severe osteoporosis, diabetes, hypertension after recent gastrointestinal anastomosis, and serious infection that cannot be controlled by antibiotics; 4. serious underlying diseases, such as cardiac dysfunction, arrhythmia, and coagulation disorders; 5. premorbid mRS ≥ 3.

Locations (1)

Xuanwu Hospital of Capital Medical University

Beijing, Beijing Municipality, China

Outcomes

Primary Outcomes

proportion of subjects achieving functional improvement

Functional improvement is defined as a decrease of at least 1 point in mRS score, modified Rankin Scale: 0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead.

Time frame: 3 months following Immunotherapy

Secondary Outcomes

modified Rankin Scale

modified Rankin Scale: 0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead.

Time frame: 3 months following Immunotherapy

modified Rankin Scale

Time frame: 6 months following Immunotherapy

modified Rankin Scale

Data from ClinicalTrials.gov

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