Teratoma Removal, Steroid, IVIG, Rituximab and Tocilizumab (T-SIRT) in Anti-NMDAR Encephalitis

• Published in: Neurotherapeutics Vol. 18; no. 1; pp. 474 - 487
• Main Authors: Lee, Woo-Jin, Lee, Soon-Tae, Shin, Yong-Won, Lee, Han Sang, Shin, Hye-Rim, Kim, Do-Yong, Kim, Soyun, Lim, Jung-Ah, Moon, Jangsup, Park, Kyung-Il, Kim, Hee Seung, Chu, Kon, Lee, Sang Kun
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2021; Springer Nature B.V
• Subjects: Adolescent; Adult; Adverse events; Aged; Anti-N-Methyl-D-Aspartate Receptor Encephalitis - therapy; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - therapeutic use; Biomedical and Life Sciences; Biomedicine; Child; Combined Modality Therapy; Drug Therapy, Combination; Encephalitis; Epilepsy; Female; Glutamic acid receptors; Humans; Immunoglobulins; Immunoglobulins, Intravenous - therapeutic use; Immunosuppressive agents; Immunotherapy; Intravenous administration; Male; Medical prognosis; Middle Aged; Monoclonal antibodies; N-Methyl-D-aspartic acid receptors; Neurobiology; Neurology; Neurosciences; Neurosurgery; Neutropenia; Original; Original Article; Ovarian Neoplasms - surgery; Patient Acuity; Patients; Population studies; Rituximab; Rituximab - administration & dosage; Rituximab - therapeutic use; Teratoma; Teratoma - surgery; Testicular Neoplasms - surgery; Treatment Outcome; Young Adult; autoimmune encephalitis; ovarian teratoma; Anti-N-methyl; aspartate receptor; prognosis; immunotherapy; Anti-N-methyl-D-aspartate receptor
• ISSN: 1933-7213; 1878-7479; 1878-7479
• DOI: 10.1007/s13311-020-00921-7

In anti-N-methyl- d -aspartate receptor (NMDAR) encephalitis, we analysed the efficacy of a combined immunotherapy protocol consisting of teratoma removal, steroid, intravenous immunoglobulin (IVIG), rituximab and tocilizumab (T-SIRT). This cohort study included seventy-eight consecutive patients treated for anti-NMDAR encephalitis between Jan 2014 and Oct 2019 in a national referral hospital. Detailed 2-year disease time course was analysed using Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores at every 2 weeks for 12 weeks from baseline, every month for the next 3 months and then every 3 months. Treatment regimens at each time point were categorized as SI, SIR, or SIRT with/without teratoma removal (T). Adverse events were classified according to the Common Terminology Criteria for Adverse-Events (CTCAE v5.0), where a severe adverse event was defined as an adverse event with CATAE grade 4. In a linear mixed model analysis, using the SIRT regimen was more effective than SIR or SI regimens in lowering CASE scores ( P  < 0.001 and P  = 0.001, respectively). The presence of teratoma ( P  = 0.001), refractory status epilepticus ( P  < 0.001) and a higher CASE score at baseline ( P  < 0.001) predicted a higher CASE score at each time point. Completion of the (T)-SIRT regimen within 1 month of onset resulted in better 1-year improvements in CASE score ( P  < 0.001) and modified Rankin scale scores ( P  = 0.001), compared to those of using other regimens within 1 month or delaying teratoma removal for more than 1 month. Pneumonia was a frequent adverse event (52/78, 66.7%) in the whole study population and neutropenia was frequent during SIRT (11/52, 21.2%), but the regimen was well tolerated in most patients. We concluded that the early application of combined immunotherapy consisting of T-SIRT had better efficacy than was found for delayed or partial application of this combination in anti-NMDAR encephalitis.