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Experts currently recommend staged immunotherapeutic management, with first\u2010line immunotherapy followed by second\u2010line immunotherapy if response to first\u2010line therapy is inadequate. Meta\u2010analysis of the evidence base may provide higher quality evidence to support this recommendation. We undertook a systematic review of observational cohort studies reporting AE patients treated with either second\u2010line immunotherapy or first\u2010line immunotherapy alone, and outcomes reported using the modified Rankin Scale (mRS; search date: April 22, 2020). We performed several one\u2010stage multilevel individual patient data (IPD) meta\u2010analyses to examine the association between second\u2010line immunotherapy and final mRS scores (PROSPERO ID CRD42020181805). IPD were obtained for 356 patients from 25 studies. Most studies were rated as moderate to high risk of bias. Seventy\u2010one patients (71\/356, 19%) were treated with second\u2010line immunotherapy. We did not find a statistically significant association between treatment with second\u2010line immunotherapy and final mRS score for the cohort overall (odds ratio [OR] =\u20091.74, 95% confidence interval [CI] = .98\u20133.08, <jats:italic>p<\/jats:italic>\u00a0=\u2009.057), or subgroups with anti\u2010N\u2010methyl\u2010D\u2010aspartate receptor encephalitis (OR\u00a0=\u00a01.03, 95% CI = .45\u20132.38, <jats:italic>p<\/jats:italic>\u00a0=\u2009.944) or severe AE (maximum mRS score\u2009&gt;\u20092; OR\u00a0=\u00a01.673, 95% CI = .93\u20133.00, <jats:italic>p<\/jats:italic>\u00a0=\u2009.085). Treatment with second\u2010line immunotherapy was associated with higher final mRS scores in subgroups with anti\u2010leucine\u2010rich glioma\u2010inactivated 1 AE (OR\u00a0=\u00a06.70, 95% CI\u00a0=\u00a01.28\u201335.1, <jats:italic>p<\/jats:italic>\u00a0=\u2009.024) and long\u2010term (at least 12\u2009months) follow\u2010up (OR\u00a0=\u00a03.94, 95% CI\u00a0=\u00a01.67\u20139.27, <jats:italic>p<\/jats:italic>\u00a0=\u2009.002). We did not observe an association between treatment with second\u2010line immunotherapy and lower final mRS scores in patients with AE. This result should be interpreted with caution, given the risk of bias, limited adjustment for disease severity, and insensitivity of the mRS in estimating psychiatric and cognitive disability.<\/jats:p>","DOI":"10.1111\/epi.17327","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T16:53:32Z","timestamp":1655225612000},"page":"2214-2224","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Second\u2010line immunotherapy and functional outcomes in autoimmune encephalitis: A systematic review and individual patient data meta\u2010analysis"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6032-4347","authenticated-orcid":false,"given":"Amy","family":"Halliday","sequence":"first","affiliation":[{"name":"Department of Medicine St Vincents Hospital Melbourne, University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Clinical Neurosciences St Vincent's Hospital Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Duncan","sequence":"additional","affiliation":[{"name":"Department of Medicine St Vincents Hospital Melbourne, University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Clinical Neurosciences St Vincent's Hospital Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Psychology National University of Singapore  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray C.","family":"Boston","sequence":"additional","affiliation":[{"name":"Department of Medicine St Vincents Hospital Melbourne, University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metha","family":"Apiwattanakul","sequence":"additional","affiliation":[{"name":"Prasat Neurological Institute  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximena","family":"Camacho","sequence":"additional","affiliation":[{"name":"Melbourne School of Population and Global Health University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Bowden","sequence":"additional","affiliation":[{"name":"Melbourne School of Psychological Sciences University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendyl","family":"D'Souza","sequence":"additional","affiliation":[{"name":"Department of Medicine St Vincents Hospital Melbourne, University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Clinical Neurosciences St Vincent's Hospital Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1708712"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010020\u201000989\u2010x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000449"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003009"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000891"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou030"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(12)70310\u20101"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.2015.1115720"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102020\u2010325300"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(10)70253\u20102"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(15)00401\u20109"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000258355.23810.c6"},{"key":"e_1_2_10_14_1","unstructured":"WellsGA SheaB O'ConnellD PetersonJ WelchV LososM et al.The Newcastle\u2010Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta\u2010analyses.http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp. 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