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

Marius Ringelstein 1, 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 
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.
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https://hal-amu.archives-ouvertes.fr/hal-03538438
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Submitted on : Friday, January 21, 2022 - 9:33:45 AM
Last modification on : Tuesday, November 22, 2022 - 2:26:16 PM

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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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