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

Marius Ringelstein 1, 2 Ilya Ayzenberg 3, 4 Gero Lindenblatt 5 Katinka Fischer 1 Anna Gahlen 3 Giovanni Novi 6 Helen Hayward-Könnecke 7 Sven Schippling 7 Paulus Rommer 8 Barbara Kornek 8 Tobias Zrzavy 8 Damien Biotti 9, 10 Jonathan Ciron 9, 10 Bertrand Audoin 11, 12, 13 Achim Berthele 14 Katrin Giglhuber 14 Helene Zephir 15 Tania Kümpfel 16 Robert Berger 17 Joachim Röther 17 Vivien Häussler 18 Jan-Patrick Stellmann 12, 13 Daniel Whittam 19 Anu Jacob 19, 20 Markus Kraemer 1, 21 Antoine Gueguen 22 Romain Deschamps 22 Antonios Bayas 23 Martin Hümmert 24 Corinna Trebst 24 Axel Haarmann 25 Sven Jarius 26 Brigitte Wildemann 26 Matthias Grothe 27 Nadja Siebert 28 Klemens Ruprecht 29 Friedemann Paul 28 Nicolas Collongues 30 Romain Marignier 31 Michael Levy 32 Michael Karenfort 33 Michael Deppe 34 Philipp Albrecht 1 Kerstin Hellwig 3 Ralf Gold 3 Hans-Peter Hartung 1 Sven Meuth 1 Ingo Kleiter 3 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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Submitted on : Friday, January 21, 2022 - 9:33:45 AM
Last modification on : Monday, July 4, 2022 - 8:53:31 AM

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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, American Academy of neurology, 2021, 9 (1), pp.e1100. ⟨10.1212/NXI.0000000000001100⟩. ⟨hal-03538438⟩

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