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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 &lt; 0.001 and P = 0.001, respectively). The presence of teratoma (P = 0.001), refractory status epilepticus (P &lt; 0.001) and a higher CASE score at baseline (P &lt; 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 &lt; 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.

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