To analyze the efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients with autoimmune encephalitis refractory to previous immunotherapies

Autoimmune encephalitis with intrathecal pathogenesis is more resistant to conventional immunotherapies with low blood-brain barrier (BBB) penetrance. Tofacitinib is a Janus kinase inhibitor used against refractory systemic immune-mediated diseases and effectively penetrates BBB. The efficacy of tofacitinib has not been investigated in autoimmune encephalitis.

From a prospective cohort in Seoul National University Hospital for autoimmune encephalitis, we retrospectively analyzed patients treated with tofacitinib. Tofacitinib was administered 5 mg per oral twice a day. Clinical response was categorized by Clinical Global Impression-Improvement scale (CGI-I) and Clinical Assessment Scale in Autoimmune Encephalitis (CASE).  A good response (CGI-I 1 or 2) was defined as a decrease in the CASE score of 5 points or more,  or cessation of clinical and electrographic seizures. 

A total of eight patients received tofacitinib for autoimmune encephalitis. All patients showed insufficient responses to previous immunotherapies including high-dose corticosteroid, intravenous immunoglobulin, rituximab, tocilizumab, and other conventional immunosuppressing agents. Among them, two had a good response (CGI-I 1or 2), three had a partial response (CGI-I 3), and the rest showed no significant improvement (CGI-I 4) to tofacitinib. One had mild nausea and one nonfatal afebrile neutropenia. A 70-year-old male with chronic meningoencephalitis featured with fluctuating steroid-dependent neurological symptoms (memory decline, altered mentality, and CSF pleocytosis) showed complete remission after the tofacitinib treatment. A 24-year-old male with MOG antibody had refractory new-onset refractory status epilepticus (NORSE) to anesthetics and immunotherapies, but the tofacitinib treatment ended the NORSE.

Our findings show the potential of tofacitinib as a therapeutic option for refractory autoimmune encephalitis. A further prospective controlled study is warranted in a larger number of patients, and it should focus on elucidating the clinical or pathogenic characteristics of tofacitinib responders.