title: Tocilizumab in Autoimmune Encephalitis Refractory to Rituximab: An Institutional Cohort Study.
abstract: A considerable portion of autoimmune encephalitis (AE) does not respond to conventional immunotherapies and subsequently has poor outcomes. We aimed to determine the efficacy of tocilizumab, an anti-interleukin-6 antibody, in rituximab-refractory AE compared with other treatment options. From an institutional cohort of AE, 91 patients with inadequate clinical response to first-line immunotherapy and following rituximab were retrospectively reviewed. Patients were grouped according to their further immunotherapy strategies. Thirty (33.0 %) patients were included in the tocilizumab group, 31 (34.0 %) in the additional rituximab group, and 30 (33.0 %) in the observation group. Outcomes were defined as the favorable modified Rankin Scale scores (≤2) at 1 and 2 months from the initiation of each treatment strategy and at the last follow-up. Favorable clinical response (improvement of the modified Rankin Scale scores by ≥ 2 points or achievement of the mRS scores ≤ 2) at the last follow-up was also analyzed. The tocilizumab group showed more frequent favorable mRS scores at 2 months from treatment initiation and at the last follow-up compared with those at the relevant time points of the remaining groups. The majority (89.5 %) of the patients with clinical improvement at 1 month from tocilizumab treatment maintained a long-term favorable clinical response. No serious adverse effects of rituximab or tocilizumab were reported. Therefore, we suggest that tocilizumab might be a good treatment strategy for treating AE refractory to conventional immunotherapies and rituximab. The tocilizumab-mediated clinical improvement manifests as early at 1 month after treatment initiation.
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Woo-Jin
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Jangsup
authors.initials: J
authors.lastname: Moon
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Jun-Sang
authors.initials: JS
authors.lastname: Sunwoo
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Jung-Ick
authors.initials: JI
authors.lastname: Byun
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Jung-Ah
authors.initials: JA
authors.lastname: Lim
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Yong-Won
authors.initials: YW
authors.lastname: Shin
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Keon-Joo
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Jin-Sun
authors.initials: JS
authors.lastname: Jun
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Han Sang
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Soyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea.
authors.forename: Kyung-Il
authors.initials: KI
authors.lastname: Park
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Jung
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea. sangkun2923@gmail.com.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea. sangkun2923@gmail.com.
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Neurology, Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea. stemcell.snu@gmail.com.|Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea. stemcell.snu@gmail.com.
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004660:Encephalitis / Q000188:drug therapy*; D005260:Female; D050031:Hashimoto Disease / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab / Q000009:adverse effects*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab; C502936:tocilizumab
keywords: Autoimmune disorders; encephalitis; immunotherapy; prognosis; tocilizumab