Rituximab Treatment and Long-term Outcome of Patients With Autoimmune Encephalitis: Real-world Evidence From the GENERATE Registry.
Adult
Aged
Anti-N-Methyl-D-Aspartate Receptor Encephalitis
/ drug therapy
Autoantibodies
/ immunology
Autoimmune Diseases of the Nervous System
/ drug therapy
Encephalitis
/ drug therapy
Female
Follow-Up Studies
Humans
Immunosuppressive Agents
/ administration & dosage
Male
Middle Aged
Outcome Assessment, Health Care
Registries
Rituximab
/ administration & dosage
Journal
Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
12
02
2021
accepted:
23
08
2021
entrez:
2
10
2021
pubmed:
3
10
2021
medline:
5
2
2022
Statut:
epublish
Résumé
To determine the real-world use of rituximab in autoimmune encephalitis (AE) and to correlate rituximab treatment with the long-term outcome. Patients with NMDA receptor (NMDAR)-AE, leucine-rich glioma-inactivated-1 (LGI1)- AE, contactin-associated protein-like-2 (CASPR2)-AE, or glutamic acid decarboxylase 65 (GAD65) disease from the GErman Network for Research on AuToimmune Encephalitis who had received at least 1 rituximab dose and a control cohort of non-rituximab-treated patients were analyzed retrospectively. Of the 358 patients, 163 (46%) received rituximab (NMDAR-AE: 57%, CASPR2-AE: 44%, LGI1-AE: 43%, and GAD65 disease: 37%). Rituximab treatment was initiated significantly earlier in NMDAR- and LGI1-AE (median: 54 and 155 days from disease onset) compared with CASPR2-AE or GAD65 disease (median: 632 and 1,209 days). Modified Rankin Scale (mRS) scores improved significantly in patients with NMDAR-AE, both with and without rituximab treatment. Although being more severely affected at baseline, rituximab-treated patients with NMDAR-AE more frequently reached independent living (mRS score ≤2) (94% vs 88%). In LGI1-AE, rituximab-treated and nontreated patients improved, whereas in CASPR2-AE, only rituximab-treated patients improved significantly. No improvement was observed in patients with GAD65 disease. A significant reduction of the relapse rate was observed in rituximab-treated patients (5% vs 13%). Detection of NMDAR antibodies was significantly associated with mRS score improvement. A favorable outcome was also observed with early treatment initiation. We provide real-world data on immunosuppressive treatments with a focus on rituximab treatment for patients with AE in Germany. We suggest that early and short-term rituximab therapy might be an effective and safe treatment option in most patients with NMDAR-, LGI1-, and CASPR2-AE. This study provides Class IV evidence that rituximab is an effective treatment for some types of AE.
Sections du résumé
BACKGROUND AND OBJECTIVES
To determine the real-world use of rituximab in autoimmune encephalitis (AE) and to correlate rituximab treatment with the long-term outcome.
METHODS
Patients with NMDA receptor (NMDAR)-AE, leucine-rich glioma-inactivated-1 (LGI1)- AE, contactin-associated protein-like-2 (CASPR2)-AE, or glutamic acid decarboxylase 65 (GAD65) disease from the GErman Network for Research on AuToimmune Encephalitis who had received at least 1 rituximab dose and a control cohort of non-rituximab-treated patients were analyzed retrospectively.
RESULTS
Of the 358 patients, 163 (46%) received rituximab (NMDAR-AE: 57%, CASPR2-AE: 44%, LGI1-AE: 43%, and GAD65 disease: 37%). Rituximab treatment was initiated significantly earlier in NMDAR- and LGI1-AE (median: 54 and 155 days from disease onset) compared with CASPR2-AE or GAD65 disease (median: 632 and 1,209 days). Modified Rankin Scale (mRS) scores improved significantly in patients with NMDAR-AE, both with and without rituximab treatment. Although being more severely affected at baseline, rituximab-treated patients with NMDAR-AE more frequently reached independent living (mRS score ≤2) (94% vs 88%). In LGI1-AE, rituximab-treated and nontreated patients improved, whereas in CASPR2-AE, only rituximab-treated patients improved significantly. No improvement was observed in patients with GAD65 disease. A significant reduction of the relapse rate was observed in rituximab-treated patients (5% vs 13%). Detection of NMDAR antibodies was significantly associated with mRS score improvement. A favorable outcome was also observed with early treatment initiation.
DISCUSSION
We provide real-world data on immunosuppressive treatments with a focus on rituximab treatment for patients with AE in Germany. We suggest that early and short-term rituximab therapy might be an effective and safe treatment option in most patients with NMDAR-, LGI1-, and CASPR2-AE.
CLASS OF EVIDENCE
This study provides Class IV evidence that rituximab is an effective treatment for some types of AE.
Identifiants
pubmed: 34599001
pii: 8/6/e1088
doi: 10.1212/NXI.0000000000001088
pmc: PMC8488759
pii:
doi:
Substances chimiques
Autoantibodies
0
Immunosuppressive Agents
0
anti-CASPR2 autoantibody
0
anti-GAD65 autoantibody
0
anti-NMDA receptor autoantibody
0
anti-leucine-rich glioma-inactivated 1 autoantibody
0
Rituximab
4F4X42SYQ6
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
Michael Adelmann
(M)
Luise Appeltshauser
(L)
Ilya Ayzenberg
(I)
Carolin Baade-Büttner
(C)
Andreas van Baalen
(A)
Sebastian Baatz
(S)
Bettina Balint
(B)
Sebastian Bauer
(S)
Annette Baumgartner
(A)
Sonka Benesch
(S)
Robert Berger
(R)
Sascha Berning
(S)
Sarah Bernsen
(S)
Christian Bien
(C)
Corinna Bien
(C)
Andreas Binder
(A)
Stefan Bittner
(S)
Daniel Bittner
(D)
Franz Blaes
(F)
Astrid Blaschek
(A)
Justina Dargvainiene
(J)
Andre Dik
(A)
Mona Dreesmann
(M)
Friedrich Ebinger
(F)
Lena Edelhoff
(L)
Sven Ehrlich
(S)
Katharina Eisenhut
(K)
Dominique Endres
(D)
Marina Entscheva
(M)
Jürgen Hartmut Faiss
(JH)
Walid Fazeli
(W)
Alexander Finke
(A)
Dirk Fitzner
(D)
Marina Flotats-Bastardas
(M)
Friedemann Paul
(F)
Manuel Friese
(M)
Marco Gallus
(M)
Marcel Gebhard
(M)
Christian Geis
(C)
Anna Gorsler
(A)
Armin Grau
(A)
Oliver Grauer
(O)
Catharina Groß
(C)
Halime Gül
(H)
Robert Handreka
(R)
Niels Hansen
(N)
Martin Häusler
(M)
Joachim Havla
(J)
Chung Ha-Yeun
(C)
Wolfgang Heide
(W)
Valentin Held
(V)
Kerstin Hellwig
(K)
Philip Hillebrand
(P)
Frank Hoffmann
(F)
Ulrich Hofstadt-van Oy
(UH)
Fatme Seval Ismail
(FS)
Martina Jansen
(M)
Max Kaufmann
(M)
Christoph Kellinghaus
(C)
Susanne Knake
(S)
Peter Körtvelyessy
(P)
Stjepana Kovac
(S)
Markus Krämer
(M)
Christos Krogias
(C)
Christoph Lehrich
(C)
Andreas Linsa
(A)
Jan Lünemann
(J)
Michael Malter
(M)
Kristin Stefanie Melzer
(KS)
Til Menge
(T)
Sven Meuth
(S)
Gerd Meyer Zu Hörste
(G)
Constanze Mönig
(C)
Marie-Luise Mono
(ML)
Michael Nagel
(M)
Tobias Neumann-Haefelin
(T)
Jost Obrocki
(J)
Thomas Pfefferkorn
(T)
Alexandra Philipsen
(A)
Johannes Piepgras
(J)
Felix von Podewils
(F)
Josef Priller
(J)
Anne-Katrin Pröbstel
(AK)
Johanna Maria Helena Rau
(JM)
Saskia Jania Räuber
(SJ)
Gernot Reimann
(G)
Raphael Reinecke
(R)
Marius Ringelstein
(M)
Hendrik Rohner
(H)
Felix Rosenow
(F)
Kevin Rostásy
(K)
Stephan Rüegg
(S)
Jens Schaumberg
(J)
Jens Schmidt
(J)
Ina-Isabelle Schmütz
(II)
Stephan Schreiber
(S)
Gesa Schreyer
(G)
Ina Schröder
(I)
Simon Schuster
(S)
Günter Seidel
(G)
Makbule Senel
(M)
Kai Siebenbrodt
(K)
Oliver Stammel
(O)
Martin Stangel
(M)
Henning Stolze
(H)
Muriel Stoppe
(M)
Karin Storm Van's Gravesande
(K)
Steffen Sybre
(S)
Simone Tauber
(S)
Florian Then Bergh
(FT)
Corinna Trebst
(C)
George Trendelenburg
(G)
Regina Trollmann
(R)
Hayrettin Tumani
(H)
Methab Türedi
(M)
Matthias von Mering
(M)
Judith Wagner
(J)
Robert Weissert
(R)
Heinz Wiendl
(H)
Brigitte Wildemann
(B)
Karsten Witt
(K)
Sigrid Wöpking
(S)
Benjamin Wunderlich
(B)
Lara Zieger
(L)
Informations de copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
Lancet Neurol. 2013 Feb;12(2):157-65
pubmed: 23290630
Neurology. 2001 Sep 11;57(5):780-4
pubmed: 11552003
Expert Rev Neurother. 2015;15(12):1391-419
pubmed: 26559389
N Engl J Med. 2008 Feb 14;358(7):676-88
pubmed: 18272891
Neurology. 2016 Oct 4;87(14):1449-1456
pubmed: 27590293
J Neuroimmunol. 2019 Dec 15;337:577063
pubmed: 31525619
Ther Adv Neurol Disord. 2021 Mar 30;14:17562864211003486
pubmed: 33854562
Lancet Neurol. 2016 Apr;15(4):391-404
pubmed: 26906964
Brain. 2010 Sep;133(9):2734-48
pubmed: 20663977
J Neurol. 1999 Aug;246(8):731-5
pubmed: 10460456
Curr Treat Options Neurol. 2003 Jan;5(1):79-90
pubmed: 12521565
Neurology. 2016 May 3;86(18):1683-91
pubmed: 27037228
Arch Neurol. 2012 Feb;69(2):230-8
pubmed: 22332190
JAMA Neurol. 2014 Aug;71(8):1009-16
pubmed: 24934144
Nat Rev Neurol. 2020 Jul;16(7):353-365
pubmed: 32457440
JAMA Neurol. 2014 Jul 1;71(7):896-900
pubmed: 24842754
Ann Neurol. 2017 Aug;82(2):271-277
pubmed: 28749549
Seizure. 2015 Aug;30:57-63
pubmed: 26216686
Ann Neurol. 2011 May;69(5):892-900
pubmed: 21416487
Cerebellum Ataxias. 2015 Nov 10;2:14
pubmed: 26561527
J Neuroimmunol. 2013 Dec 15;265(1-2):75-81
pubmed: 24176648
JAMA Neurol. 2015 Nov;72(11):1304-12
pubmed: 26414229
Epilepsy Behav. 2018 Mar;80:331-336
pubmed: 29433947
Lancet Neurol. 2010 Aug;9(8):776-85
pubmed: 20580615
Ann N Y Acad Sci. 2015 Mar;1338:94-114
pubmed: 25315420
Neurology. 2016 Aug 23;87(8):759-65
pubmed: 27466467
PLoS One. 2015 Mar 16;10(3):e0121364
pubmed: 25774787
J Neurol. 2014 Jan;261(1):1-16
pubmed: 24272588
Neurology. 2011 Jul 12;77(2):179-89
pubmed: 21747075
J Neurol. 2020 Jul;267(7):2101-2114
pubmed: 32246252
Lancet Neurol. 2008 Dec;7(12):1091-8
pubmed: 18851928
J Neurol Sci. 1996 Nov;143(1-2):57-9
pubmed: 8981298
Ann Neurol. 2020 Feb;87(2):313-323
pubmed: 31782181
Ann Neurol. 2012 Aug;72(2):241-55
pubmed: 22473710
Acta Neurol Scand. 2020 Nov;142(5):449-459
pubmed: 32484900