efficacy and safety of taitacept in treatment of refractory or recurrent anti-nmdar/anti-lgi1 encephalitis

Conditions: Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Summary: the main objective is to explore the efficacy and safety of telitacicept in the treatment of refractory/recurrent anti-nmdar and anti-lgi1 encephalitis. through this prospective, single-center, open-label clinical trial, we aim to investigate the effectiveness and safety of telitacicept in refractory/recurrent anti-nmdar and anti-lgi1 encephalitis by add-on therapy of telitacicept combined with traditional treatment.


Eligibility criteria:
inclusion criteria: 1. age ≥14 years old, male or female; 2. symptoms of autoimmune encephalitis (ae) ≤ 9 months prior to enrollment; 3. diagnosed as autoimmune encephalitis, diagnostic criteria as follows: 1. rapid onset (\<3 months) of at least four of the following six major symptoms: * abnormal (mental) behavior or cognitive dysfunction * speech dysfunction (verbal urgency, hypospeech, mutism) * seizures * movement disorders, dyskinesias, or postural rigidity/abnormalities * decreased level of consciousness * autonomic dysfunction or central hypoventilation in the presence of one or more of the six major symptoms; 2. positive anti-nmdar (glun1) igg antibody detected in csf or positive serum and/or cerebrospinal fluid lgi1 antibody; c．reasonable exclusion of other etiologies and other well-defined encephalitis syndromes (e.g., bickerstaff brainstem encephalitis, acute disseminated encephalomyelitis, hashimoto encephalopathy, primary cns vasculitis, rasmussen encephalitis); 4. refractory ae: ineffective treatment with steroids and rituximab or other immunosuppressants, post-treatment mrs score≥2 (stable for at least 24 hours）;recurrent ae: at least 2 months after 1st or 2nd line treatment, new symptoms or worsening of existing symptoms (mrs increase\>1); 5）doses of steroids and other immunosuppressants (e.g. azathioprine, mycophenolate mofetil, cyclophosphamide) should be stabilised for 4 weeks prior to enrolment; 6）ability to obtain patient or proxy consent; 7）women of childbearing potential should use effective contraception during treatment or avoid heterosexual intercourse for at least 3 months after the last dose of talitacicept; exclusion criteria: 1. history of other autoimmunity such as sle, ra, ss. patients with hyperthyroidism and hypothyroidism cannot be excluded; 2. abnormal laboratory indicators, including but not limited to the following indicators: white blood cell count\ 1.5×uln tbil(total bilirubin) \>1.5×uln alt\>3× uln ast\>3× uln alkaline phosphatase\>2× uln creatine kinase\>5× uln 3. evidence of active infection such as shingles, hiv or active tuberculosis, etc. 4. currently have active hepatitis or have severe liver disease and a history of it. * patiens with abnormal hepatitis b test as follows should be excluded: hbsag positive; hbsag negative but hbcab positive, and hbv-dna positive. whereas patients with hbsag negative but hbcab positive, and hbv-dna negative can be included. * exclude patients who are positive for hepatitis c antibodies ; 5. uncontrolled diabetes mellitus: glycosylated hemoglobin\>9.0% or fasting blood glucose≥11.1mmol/l; 6. received any live vaccine within 3 months prior to enrollment or planned to receive any vaccine during the study; 7. received rituximab or other biological therapies within 1 month prior to enrollment; 8. malignancy; 9. allergic to human biological products; 10. participated in any clinical trial within 28 days prior to enrollment or within 5 times the half-life of the investigational drug participating in the clinical trial 11. patients who plan to have children during the trial, or who are pregnant or breastfeeding; 12. alcohol or drug abuse/addiction is known to have an impact on compliance with trial requirements; 13. patients who are deemed unsuitable for the trial by the investigator (e.g., those with severe mental disorders).