Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG–Associated Disease and Neuromyelitis Optica Spectrum Disorders
Marius Ringelstein
(1)
,
Ilya Ayzenberg
(2, 3)
,
Gero Lindenblatt
(4)
,
Katinka Fischer
(1)
,
Anna Gahlen
(2)
,
Giovanni Novi
(5)
,
Helen Hayward-Könnecke
(6)
,
Sven Schippling
(6)
,
Paulus Rommer
(7)
,
Barbara Kornek
(7)
,
Tobias Zrzavy
(7)
,
Damien Biotti
(8, 9)
,
Jonathan Ciron
(8, 9)
,
Bertrand Audoin
(10, 11, 12)
,
Achim Berthele
(13)
,
Katrin Giglhuber
(13)
,
Helene Zephir
(14)
,
Tania Kümpfel
(15)
,
Robert Berger
(16)
,
Joachim Röther
(16)
,
Vivien Häussler
(17)
,
Jan-Patrick Stellmann
(11, 12)
,
Daniel Whittam
(18)
,
Anu Jacob
(18, 19)
,
Markus Kraemer
(1, 20)
,
Antoine Gueguen
(21)
,
Romain Deschamps
(21)
,
Antonios Bayas
(22)
,
Martin Hümmert
(23)
,
Corinna Trebst
(23)
,
Axel Haarmann
(24)
,
Sven Jarius
(25)
,
Brigitte Wildemann
(25)
,
Matthias Grothe
(26)
,
Nadja Siebert
(27)
,
Klemens Ruprecht
(28)
,
Friedemann Paul
(27)
,
Nicolas Collongues
(29)
,
Romain Marignier
(30)
,
Michael Levy
(31)
,
Michael Karenfort
(1)
,
Michael Deppe
(32)
,
Philipp Albrecht
(1)
,
Kerstin Hellwig
(2)
,
Ralf Gold
(2)
,
Hans-Peter Hartung
(1)
,
Sven Meuth
(1)
,
Ingo Kleiter
(2)
,
Orhan Aktas
(1)
1
Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]
2 RUB - Ruhr University Bochum = Ruhr-Universität Bochum
3 Department of Neurology Sechenov First Moscow State Medical University, Russia
4 Department of Neurology Johanna Etienne Hospital, Neuss, Germany
5 Department of Neurology San Martino Hospital, Genova, Italy
6 University hospital of Zurich [Zurich]
7 Medizinische Universität Wien = Medical University of Vienna
8 Département Neurologie [CHU Toulouse]
9 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
10 Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM]
11 CRMBM - Centre de résonance magnétique biologique et médicale
12 CEMEREM - Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM]
13 MRI TUM - Klinikum rechts der Isar
14 Université de Lille
15 Institute of Clinical Neuroimmunology, Faculty of Medicine, Ludwig Maximilian University, Munich
16 Department of Neurology, Asklepios Klinik Altona, Hamburg
17 Department of Neurology and Institute of Neuroimmunology and MS (INIMS), University Medical Center Hamburg-Eppendorf, Germany
18 Department of Neurology, The Walton Centre, Liverpool, United Kingdom
19 the Cleveland Clinic Abu Dhabi, UAE
20 Department of Neurology, Alfried Krupp Hospital, Essen, Germany
21 Department of Neurology, Fondation Ophtalmologique Adolphe de Rothschild, Paris, France
22 Department of Neurology, Universitätsklinikum Augsburg
23 Department of Neurology, Hannover Medical School
24 JMU - Julius-Maximilians-Universität Würzburg = University of Würzburg
25 Universität Heidelberg [Heidelberg] = Heidelberg University
26 Department of Neurology, University hospital Greifswald
27 NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité Universitätsmedizin Berlin
28 Freie Universität Berlin
29 Department of Neurology, University Hospital Strasbourg
30 Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation - Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France
31 Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston
32 Department of Neurology, University Hospital, Münster
2 RUB - Ruhr University Bochum = Ruhr-Universität Bochum
3 Department of Neurology Sechenov First Moscow State Medical University, Russia
4 Department of Neurology Johanna Etienne Hospital, Neuss, Germany
5 Department of Neurology San Martino Hospital, Genova, Italy
6 University hospital of Zurich [Zurich]
7 Medizinische Universität Wien = Medical University of Vienna
8 Département Neurologie [CHU Toulouse]
9 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
10 Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM]
11 CRMBM - Centre de résonance magnétique biologique et médicale
12 CEMEREM - Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM]
13 MRI TUM - Klinikum rechts der Isar
14 Université de Lille
15 Institute of Clinical Neuroimmunology, Faculty of Medicine, Ludwig Maximilian University, Munich
16 Department of Neurology, Asklepios Klinik Altona, Hamburg
17 Department of Neurology and Institute of Neuroimmunology and MS (INIMS), University Medical Center Hamburg-Eppendorf, Germany
18 Department of Neurology, The Walton Centre, Liverpool, United Kingdom
19 the Cleveland Clinic Abu Dhabi, UAE
20 Department of Neurology, Alfried Krupp Hospital, Essen, Germany
21 Department of Neurology, Fondation Ophtalmologique Adolphe de Rothschild, Paris, France
22 Department of Neurology, Universitätsklinikum Augsburg
23 Department of Neurology, Hannover Medical School
24 JMU - Julius-Maximilians-Universität Würzburg = University of Würzburg
25 Universität Heidelberg [Heidelberg] = Heidelberg University
26 Department of Neurology, University hospital Greifswald
27 NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité Universitätsmedizin Berlin
28 Freie Universität Berlin
29 Department of Neurology, University Hospital Strasbourg
30 Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation - Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France
31 Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston
32 Department of Neurology, University Hospital, Münster
Marius Ringelstein
- Fonction : Auteur
- PersonId : 799598
- ORCID : 0000-0001-8619-1327
Giovanni Novi
- Fonction : Auteur
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- ORCID : 0000-0003-3877-6763
Tobias Zrzavy
- Fonction : Auteur
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- ORCID : 0000-0001-8909-1591
Jonathan Ciron
- Fonction : Auteur
- PersonId : 795646
- ORCID : 0000-0002-3386-6308
- IdRef : 137599021
Achim Berthele
- Fonction : Auteur
- PersonId : 800455
- ORCID : 0000-0001-9650-6222
Tania Kümpfel
- Fonction : Auteur
- PersonId : 804025
- ORCID : 0000-0001-7509-5268
Vivien Häussler
- Fonction : Auteur
- PersonId : 805877
- ORCID : 0000-0002-7787-7391
Jan-Patrick Stellmann
- Fonction : Auteur
- PersonId : 736496
- IdHAL : jan-patrick-stellmann
- ORCID : 0000-0003-2565-2833
Matthias Grothe
- Fonction : Auteur
- PersonId : 820972
- ORCID : 0000-0002-7998-5310
Nicolas Collongues
- Fonction : Auteur
- PersonId : 764750
- ORCID : 0000-0002-3683-5582
Romain Marignier
- Fonction : Auteur
- PersonId : 1194084
- IdHAL : romain-marignier
- ORCID : 0000-0002-5967-2800
Michael Levy
- Fonction : Auteur
- PersonId : 766190
- ORCID : 0000-0002-7969-8346
Philipp Albrecht
- Fonction : Auteur
- PersonId : 800164
- ORCID : 0000-0001-7987-658X
Kerstin Hellwig
- Fonction : Auteur
- PersonId : 775629
- ORCID : 0000-0003-4467-9011
Sven Meuth
- Fonction : Auteur
- PersonId : 794901
- ORCID : 0000-0003-2571-3501
Ingo Kleiter
- Fonction : Auteur
- PersonId : 775628
- ORCID : 0000-0002-8249-4408
Orhan Aktas
- Fonction : Auteur
- PersonId : 775630
- ORCID : 0000-0002-2020-9210
Résumé
Background and Objectives To evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti–interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein–IgG–associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD). Methods Annualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab. Results Patients received TCZ for 23.8 months (median; interquartile range 13.0–51.1 months), with an IV dose of 8.0 mg/kg (median; range 6–12 mg/kg) every 31.6 days (mean; range 26–44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5–5) to 0 (range 0–0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0–5] to 0 [range 0–4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0–3.0] to 0.2 [range 0–2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD ( p = 0.04; for the brain) and in AQP4-IgG+ NMOSD ( p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy. Discussion This study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD.
Domaines
Immunothérapie| Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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