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

Neurol Neuroimmunol Neuroinflamm

Department of Neurology (M.R., K.F., M.K.,P.A., H.P.H., S.G.M., O.A.), Medical Faculty, Heinrich Heine University Düsseldorf; Department of Neurology (M.R.), Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich Heine University Düsseldorf; Department of Neurology (I.A., A.G., K.H., R.G., I.K.), St. Josef-Hospital, Ruhr University Bochum, Germany; Department of Neurology (I.A.), Sechenov First Moscow State Medical University, Russia; Department of Neurology (G.L.), Johanna Etienne Hospital, Neuss, Germany; Department of Neurology (G.N.), San Martino Hospital, Genova, Italy; Neuroimmunology and MS Research (H.H.K., S.S.), Department of Neurology, University Hospital Zürich, Switzerland; Department of Neurology (P.S.R., B.K., T.Z.), Medical University of Vienna, Austria; Department of Neurology (D.B., J.C.), B4 unit, CRC-SEP, Toulouse Purpan University Hospital, France; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity) (D.B., J.C.) INSERM UMR1291-CNRS UMR5051 - Université Toulouse III, France; Aix Marseille University (B.A.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France; Technical University of Munich (A.B., K.G.), School of Medicine, Department of Neurology, Klinikum rechts der Isar, Germany; University of Lille (H.Z.), Inserm, CRC-SEP, CHU Lille, France; Institute of Clinical Neuroimmunology (T.K.), Faculty of Medicine, Ludwig Maximilian University, Munich; Department of Neurology (R.B., J.R.), Asklepios Klinik Altona, Hamburg; Department of Neurology and Institute of Neuroimmunology and MS (INIMS) (V.H.), University Medical Center Hamburg-Eppendorf, Germany; APHM, Hôpital de la Timone (J.P.S.), CEMEREM; Aix Marseille Univ, CNRS, CRMBM (J.P.S), UMR 7339, Marseille, France; Department of Neurology (D.W., A.J.), The Walton Centre, Liverpool, United Kingdom; the Cleveland Clinic Abu Dhabi, (A.J.) UAE; Department of Neurology (M.K.), Alfried Krupp Hospital, Essen, Germany; Department of Neurology (A.G.,R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris, France; Department of Neurology (A.B.), Universitätsklinikum Augsburg; Department of Neurology (M.W.H., C.T.), Hannover Medical School; Department of Neurology (A.H.), University of Würzburg; Molecular Neuroimmunology Group (S.J., B.W.), Department of Neurology, University of Heidelberg; Department of Neurology (M.G.), University hospital Greifswald; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (N.S., F.P), Max Delbrueck Center for Molecular Medicine and Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health; Department of Neurology (K.R.), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin; Department of Neurology (N.C.), University Hospital Strasbourg; Service de neurologie (R.M.), sclérose en plaques, pathologies de la myéline et neuro-inflammation - Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, France; Department of Neurology (M.L.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of General Pediatrics (M.K.), Neonatology and Pediatric Cardiology, University Children's Hospital, Medical Faculty, Heinrich Heine University Düsseldorf; Department of Neurology (M.D.), University Hospital, Münster; and Marianne-Strauß-Klinik (I.K.), Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg, Germany.

Published: January 2022

The study aimed to assess the long-term safety and effectiveness of tocilizumab (TCZ), an antibody that targets interleukin-6 receptors, for treating myelin oligodendrocyte glycoprotein-IgG-associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD).
Researchers reviewed data from 57 patients who switched to TCZ from other treatments, monitoring relapse rates, disability status, MRI results, and more for up to 51 months.
The results showed significant reductions in relapse rates for MOGAD and AQP4-IgG-positive patients, with many remaining relapse-free and no serious safety concerns, indicating TCZ's potential as a leading

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; = 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]; < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0-3.0] to 0.2 [range 0-2.0]; = 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 ( = 0.04; for the brain) and in AQP4-IgG+ NMOSD ( < 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596357	PMC
http://dx.doi.org/10.1212/NXI.0000000000001100	DOI Listing

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