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Journal Articles Neurology Neuroimmunology & Neuroinflammation Year : 2021

Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG–Associated Disease and Neuromyelitis Optica Spectrum Disorders

1 Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]
2 Department of Neurology St. Josef-Hospital, Ruhr University Bochum, Germany
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 Neuroimmunology and MS Research Department of Neurology, University Hospital Zürich, Switzerland
7 Department of Neurology Medical University of Vienna, Austria
8 Department of Neurology B4 unit, CRC-SEP, Toulouse Purpan University Hospital, France
9 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
10 Pôle de Neurosciences Cliniques, Service de Neurologie, APHM, Hôpital de la Timone, Aix-Marseille University, Marseille, France
11 CRMBM - Centre de résonance magnétique biologique et médicale
12 CEMEREM - Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM]
13 Technical University of Munich, School of Medicine, Department of Neurology, Klinikum rechts der Isar, Germany
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 Department of Neurology, University of Würzburg
25 Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg
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

Abstract

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.

Dates and versions

hal-03538438 , version 1 (21-01-2022)

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Marius Ringelstein, Ilya Ayzenberg, Gero Lindenblatt, Katinka Fischer, Anna Gahlen, et al.. Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG–Associated Disease and Neuromyelitis Optica Spectrum Disorders. Neurology Neuroimmunology & Neuroinflammation, 2021, 9 (1), pp.e1100. ⟨10.1212/NXI.0000000000001100⟩. ⟨hal-03538438⟩
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