cpi combination therapy for autoimmune encephalitis

Conditions: Autoimmune Encephalitis

Summary: 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.

Eligibility criteria:
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 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.

Keywords: autoimmune encephalitis, plasma exchange, immunotherapy, outcome corticosteroid immunoglobulin