Skip to main content
Erschienen in: Neurotherapeutics 4/2016

01.10.2016 | Original Article

Tocilizumab in Autoimmune Encephalitis Refractory to Rituximab: An Institutional Cohort Study

verfasst von: Woo-Jin Lee, Soon-Tae Lee, Jangsup Moon, Jun-Sang Sunwoo, Jung-Ick Byun, Jung-Ah Lim, Tae-Joon Kim, Yong-Won Shin, Keon-Joo Lee, Jin-Sun Jun, Han Sang Lee, Soyun Kim, Kyung-Il Park, Keun-Hwa Jung, Ki-Young Jung, Manho Kim, Sang Kun Lee, Kon Chu

Erschienen in: Neurotherapeutics | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 2011;77:179-189.CrossRefPubMedPubMedCentral Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 2011;77:179-189.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Zuliani L, Graus F, Giometto B, Bien C, Vincent A. Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition. J Neurol Neurosurg Psychiatry 2012:jnnp-2011-301237. Zuliani L, Graus F, Giometto B, Bien C, Vincent A. Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition. J Neurol Neurosurg Psychiatry 2012:jnnp-2011-301237.
3.
Zurück zum Zitat Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis 2012;54:899-904.CrossRefPubMedPubMedCentral Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis 2012;54:899-904.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Armangue T, Leypoldt F, Dalmau J. Autoimmune encephalitis as differential diagnosis of infectious encephalitis. Curr Opin Neurol 2014;27:361-368.CrossRefPubMedPubMedCentral Armangue T, Leypoldt F, Dalmau J. Autoimmune encephalitis as differential diagnosis of infectious encephalitis. Curr Opin Neurol 2014;27:361-368.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391-404.CrossRefPubMed Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391-404.CrossRefPubMed
6.
Zurück zum Zitat Singh TD, Fugate JE, Rabinstein AA. The spectrum of acute encephalitis causes, management, and predictors of outcome. Neurology 2015;84:359-366.CrossRefPubMed Singh TD, Fugate JE, Rabinstein AA. The spectrum of acute encephalitis causes, management, and predictors of outcome. Neurology 2015;84:359-366.CrossRefPubMed
7.
Zurück zum Zitat Hacohen Y, Wright S, Waters P, et al. Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry 2013;84:748-755.CrossRefPubMed Hacohen Y, Wright S, Waters P, et al. Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry 2013;84:748-755.CrossRefPubMed
8.
Zurück zum Zitat Lee W-J, Lee S-T, Byun J-I, et al. Rituximab treatment for autoimmune limbic encephalitis in an institutional cohort. Neurology 2016:10.1212/WNL. 0000000000002635. Lee W-J, Lee S-T, Byun J-I, et al. Rituximab treatment for autoimmune limbic encephalitis in an institutional cohort. Neurology 2016:10.​1212/​WNL. 0000000000002635.
9.
Zurück zum Zitat Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12:157-165.CrossRefPubMedPubMedCentral Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12:157-165.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Kim SJ, Lee JW, Jung CW, et al. Weekly rituximab followed by monthly rituximab treatment for steroid-refractory chronic graft-versus-host disease: results from a prospective, multicenter, phase II study. Haematologica 2010;95:1935-1942.CrossRefPubMedPubMedCentral Kim SJ, Lee JW, Jung CW, et al. Weekly rituximab followed by monthly rituximab treatment for steroid-refractory chronic graft-versus-host disease: results from a prospective, multicenter, phase II study. Haematologica 2010;95:1935-1942.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Hainsworth JD, Litchy S, Shaffer DW, Lackey VL, Grimaldi M, Greco FA. Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's lymphoma—a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2005;23:1088-1095.CrossRefPubMed Hainsworth JD, Litchy S, Shaffer DW, Lackey VL, Grimaldi M, Greco FA. Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's lymphoma—a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2005;23:1088-1095.CrossRefPubMed
12.
Zurück zum Zitat Tanaka T, Narazaki M, Kishimoto T. Anti-interleukin-6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases. FEBS Lett 2011;585:3699-3709.CrossRefPubMed Tanaka T, Narazaki M, Kishimoto T. Anti-interleukin-6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases. FEBS Lett 2011;585:3699-3709.CrossRefPubMed
13.
Zurück zum Zitat Okada M, Kitahara M, Kishimoto S, Matsuda T, Hirano T, Kishimoto T. IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol 1988;141:1543-1549.PubMed Okada M, Kitahara M, Kishimoto S, Matsuda T, Hirano T, Kishimoto T. IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol 1988;141:1543-1549.PubMed
14.
Zurück zum Zitat Kimura A, Kishimoto T. IL-6: Regulator of Treg/Th17 balance. Eur J Immunol 2010;40:1830-1835.CrossRefPubMed Kimura A, Kishimoto T. IL-6: Regulator of Treg/Th17 balance. Eur J Immunol 2010;40:1830-1835.CrossRefPubMed
15.
Zurück zum Zitat Kishimoto T. Interleukin-6: from basic science to medicine-40 years in immunology. Annu Rev Immunol 2005;23:1-21.CrossRefPubMed Kishimoto T. Interleukin-6: from basic science to medicine-40 years in immunology. Annu Rev Immunol 2005;23:1-21.CrossRefPubMed
16.
Zurück zum Zitat Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 2008;371:987-997.CrossRefPubMed Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 2008;371:987-997.CrossRefPubMed
17.
Zurück zum Zitat Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J. Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis 2009;68:1580-1584.CrossRefPubMed Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J. Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis 2009;68:1580-1584.CrossRefPubMed
18.
Zurück zum Zitat Illei GG, Shirota Y, Yarboro CH, et al. Tocilizumab in systemic lupus erythematosus: Data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum 2010;62:542-552.CrossRefPubMedPubMedCentral Illei GG, Shirota Y, Yarboro CH, et al. Tocilizumab in systemic lupus erythematosus: Data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum 2010;62:542-552.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Araki M, Matsuoka T, Miyamoto K, et al. Efficacy of the anti–IL-6 receptor antibody tocilizumab in neuromyelitis optica A pilot study. Neurology 2014;82:1302-1306.CrossRefPubMedPubMedCentral Araki M, Matsuoka T, Miyamoto K, et al. Efficacy of the anti–IL-6 receptor antibody tocilizumab in neuromyelitis optica A pilot study. Neurology 2014;82:1302-1306.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Ayzenberg I, Kleiter I, Schröder A, et al. Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy. JAMA Neurol 2013;70:394-397.CrossRefPubMed Ayzenberg I, Kleiter I, Schröder A, et al. Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy. JAMA Neurol 2013;70:394-397.CrossRefPubMed
21.
Zurück zum Zitat Ringelstein M, Ayzenberg I, Harmel J, et al. Long-term Therapy with interleukin 6 receptor blockade in highly active neuromyelitis optica spectrum disorder. JAMA Neurol 2015;72:756-763.CrossRefPubMed Ringelstein M, Ayzenberg I, Harmel J, et al. Long-term Therapy with interleukin 6 receptor blockade in highly active neuromyelitis optica spectrum disorder. JAMA Neurol 2015;72:756-763.CrossRefPubMed
22.
Zurück zum Zitat Krogias C, Hoepner R, Müller A, Schneider-Gold C, Schröder A, Gold R. Successful treatment of anti-Caspr2 syndrome by interleukin 6 receptor blockade through tocilizumab. JAMA Neurol 2013;70:1056-1059.CrossRefPubMed Krogias C, Hoepner R, Müller A, Schneider-Gold C, Schröder A, Gold R. Successful treatment of anti-Caspr2 syndrome by interleukin 6 receptor blockade through tocilizumab. JAMA Neurol 2013;70:1056-1059.CrossRefPubMed
23.
Zurück zum Zitat Irani SR, Vincent A. Targeting the interleukin 6 receptor to treat neuromyelitis optica. JAMA Neurol 2015;72:747-748.CrossRefPubMed Irani SR, Vincent A. Targeting the interleukin 6 receptor to treat neuromyelitis optica. JAMA Neurol 2015;72:747-748.CrossRefPubMed
24.
Zurück zum Zitat Venkatesan A, Tunkel A, Bloch K, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 2013;57:1114-1128.CrossRefPubMedPubMedCentral Venkatesan A, Tunkel A, Bloch K, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 2013;57:1114-1128.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Kim T-J, Lee S-T, Shin J-W, et al. Clinical manifestations and outcomes of the treatment of patients with GABA B encephalitis. J Neuroimmunol 2014;270:45-50.CrossRefPubMed Kim T-J, Lee S-T, Shin J-W, et al. Clinical manifestations and outcomes of the treatment of patients with GABA B encephalitis. J Neuroimmunol 2014;270:45-50.CrossRefPubMed
26.
Zurück zum Zitat Lim J-A, Lee S-T, Jung K-H, et al. Anti-N-methyl-d-aspartate receptor encephalitis in Korea: clinical features, treatment, and outcome. J Clin Neurol 2014;10:157-161.CrossRefPubMedPubMedCentral Lim J-A, Lee S-T, Jung K-H, et al. Anti-N-methyl-d-aspartate receptor encephalitis in Korea: clinical features, treatment, and outcome. J Clin Neurol 2014;10:157-161.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Sunwoo J-S, Lee S-T, Byun J-I, et al. Clinical manifestations of patients with CASPR2 antibodies. J Neuroimmunol 2015;281:17-22.CrossRefPubMed Sunwoo J-S, Lee S-T, Byun J-I, et al. Clinical manifestations of patients with CASPR2 antibodies. J Neuroimmunol 2015;281:17-22.CrossRefPubMed
28.
Zurück zum Zitat Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008;47:303-327.CrossRefPubMed Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008;47:303-327.CrossRefPubMed
29.
Zurück zum Zitat Gürcan HM, Keskin DB, Stern JN, Nitzberg MA, Shekhani H, Ahmed AR. A review of the current use of rituximab in autoimmune diseases. Int Immunopharmacol 2009;9:10-25.CrossRefPubMed Gürcan HM, Keskin DB, Stern JN, Nitzberg MA, Shekhani H, Ahmed AR. A review of the current use of rituximab in autoimmune diseases. Int Immunopharmacol 2009;9:10-25.CrossRefPubMed
31.
Zurück zum Zitat Dale RC, Brilot F, Duffy LV, et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology 2014;83:142-150.CrossRefPubMedPubMedCentral Dale RC, Brilot F, Duffy LV, et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology 2014;83:142-150.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Ogura H, Murakami M, Okuyama Y, et al. Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction. Immunity 2008;29:628-636.CrossRefPubMed Ogura H, Murakami M, Okuyama Y, et al. Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction. Immunity 2008;29:628-636.CrossRefPubMed
33.
Zurück zum Zitat Gijbels K, van Damme J, Proost P, Put W, Carton H, Billiau A. Interleukin 6 production in the central nervous system during experimental autoimmune encephalomyelitis. Eur J Immunol 1990;20:233-235.CrossRefPubMed Gijbels K, van Damme J, Proost P, Put W, Carton H, Billiau A. Interleukin 6 production in the central nervous system during experimental autoimmune encephalomyelitis. Eur J Immunol 1990;20:233-235.CrossRefPubMed
34.
Zurück zum Zitat Gruol D, Nelson T. Physiological and pathological roles of interleukin-6 in the central nervous system. Mol Neurobiol 1997;15:307-339.CrossRefPubMed Gruol D, Nelson T. Physiological and pathological roles of interleukin-6 in the central nervous system. Mol Neurobiol 1997;15:307-339.CrossRefPubMed
35.
Zurück zum Zitat Irani SR, Gelfand JM, Al-Diwani A, Vincent A. Cell-surface central nervous system autoantibodies: Clinical relevance and emerging paradigms. Ann Neurol 2014;76:168-184. Irani SR, Gelfand JM, Al-Diwani A, Vincent A. Cell-surface central nervous system autoantibodies: Clinical relevance and emerging paradigms. Ann Neurol 2014;76:168-184.
36.
Zurück zum Zitat McLaughlin P, Grillo-López AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998;16:2825-2833.PubMed McLaughlin P, Grillo-López AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998;16:2825-2833.PubMed
37.
Zurück zum Zitat Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol 2007;6:805-815.CrossRefPubMed Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol 2007;6:805-815.CrossRefPubMed
Metadaten
Titel
Tocilizumab in Autoimmune Encephalitis Refractory to Rituximab: An Institutional Cohort Study
verfasst von
Woo-Jin Lee
Soon-Tae Lee
Jangsup Moon
Jun-Sang Sunwoo
Jung-Ick Byun
Jung-Ah Lim
Tae-Joon Kim
Yong-Won Shin
Keon-Joo Lee
Jin-Sun Jun
Han Sang Lee
Soyun Kim
Kyung-Il Park
Keun-Hwa Jung
Ki-Young Jung
Manho Kim
Sang Kun Lee
Kon Chu
Publikationsdatum
01.10.2016
Verlag
Springer US
Erschienen in
Neurotherapeutics / Ausgabe 4/2016
Print ISSN: 1933-7213
Elektronische ISSN: 1878-7479
DOI
https://doi.org/10.1007/s13311-016-0442-6

Weitere Artikel der Ausgabe 4/2016

Neurotherapeutics 4/2016 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.