Interleukin-6 receptor blockade in treatment-refractory MOG-IgG-associated disease and neuromyelitis optica spectrum disorders

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...

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Hauptverfasser: Ringelstein, Marius (VerfasserIn) , Ayzenberg, Ilya (VerfasserIn) , Lindenblatt, Gero (VerfasserIn) , Fischer, Katinka (VerfasserIn) , Gahlen, Anna (VerfasserIn) , Novi, Giovanni (VerfasserIn) , Hayward-Könnecke, Helen (VerfasserIn) , Schippling, Sven (VerfasserIn) , Rommer, Paulus S. (VerfasserIn) , Kornek, Barbara (VerfasserIn) , Zrzavy, Tobias (VerfasserIn) , Biotti, Damien (VerfasserIn) , Ciron, Jonathan (VerfasserIn) , Audoin, Bertrand (VerfasserIn) , Berthele, Achim (VerfasserIn) , Giglhuber, Katrin (VerfasserIn) , Zephir, Helene (VerfasserIn) , Kümpfel, Tania (VerfasserIn) , Berger, Robert (VerfasserIn) , Röther, Joachim (VerfasserIn) , Häußler, Vivien (VerfasserIn) , Stellmann, Jan-Patrick (VerfasserIn) , Whittam, Daniel (VerfasserIn) , Jacob, Anu (VerfasserIn) , Kraemer, Markus (VerfasserIn) , Gueguen, Antoine (VerfasserIn) , Deschamps, Romain (VerfasserIn) , Bayas, Antonios (VerfasserIn) , Hümmert, Martin W. (VerfasserIn) , Trebst, Corinna (VerfasserIn) , Haarmann, Axel (VerfasserIn) , Jarius, Sven (VerfasserIn) , Wildemann, Brigitte (VerfasserIn) , Grothe, Matthias (VerfasserIn) , Siebert, Nadja (VerfasserIn) , Ruprecht, Klemens (VerfasserIn) , Paul, Friedemann (VerfasserIn) , Collongues, Nicolas (VerfasserIn) , Marignier, Romain (VerfasserIn) , Levy, Michael (VerfasserIn) , Karenfort, Michael (VerfasserIn) , Deppe, Michael (VerfasserIn) , Albrecht, Philipp (VerfasserIn) , Hellwig, Kerstin (VerfasserIn) , Gold, Ralf (VerfasserIn) , Hartung, Hans-Peter (VerfasserIn) , Meuth, Sven (VerfasserIn) , Kleiter, Ingo Wolfram (VerfasserIn) , Aktaş, Orhan (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2022
In: Neurology: Neuroimmunology & Neuroinflammation ; official journal of the American Academy of Neurology
Year: 2022, Jahrgang: 9, Heft: 1, Pages: 1-20
ISSN:2332-7812
DOI:10.1212/NXI.0000000000001100
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1212/NXI.0000000000001100
Verlag, lizenzpflichtig, Volltext: https://nn.neurology.org/content/9/1/e1100
Volltext
Verfasserangaben:Marius Ringelstein, MD, Ilya Ayzenberg, MD, Gero Lindenblatt, MD, Katinka Fischer, MSc, Anna Gahlen, MD, Giovanni Novi, MD, Helen Hayward-Könnecke, MD, Sven Schippling, MD, Paulus S. Rommer, MD, Barbara Kornek, MD, Tobias Zrzavy, MD, Damien Biotti, MD, Jonathan Ciron, MD, Bertrand Audoin, MD, Achim Berthele, MD, Katrin Giglhuber, MD, Helene Zephir, MD, Tania Kümpfel, MD, Robert Berger, MD, Joachim Röther, MD, Vivien Häußler, MD, Jan-Patrick Stellmann, MD, Daniel Whittam, MD, Anu Jacob, MD, Markus Kraemer, MD, Antoine Gueguen, MD, Romain Deschamps, MD, Antonios Bayas, MD, Martin W. Hümmert, MD, Corinna Trebst, MD, Axel Haarmann, MD, Sven Jarius, MD, Brigitte Wildemann, MD, Matthias Grothe, MD, Nadja Siebert, MD, Klemens Ruprecht, MD, Friedemann Paul, MD, Nicolas Collongues, MD, Romain Marignier, MD, Michael Levy, MD, Michael Karenfort, MD, Michael Deppe, PhD, Philipp Albrecht, MD, Kerstin Hellwig, MD, Ralf Gold, MD, Hans-Peter Hartung, MD, Sven G. Meuth, MD, Ingo Kleiter, MD, Orhan Aktas, MD, on behalf of the Neuromyelitis Optica Study Group (NEMOS)

MARC

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245 1 0 |a Interleukin-6 receptor blockade in treatment-refractory MOG-IgG-associated disease and neuromyelitis optica spectrum disorders  |c Marius Ringelstein, MD, Ilya Ayzenberg, MD, Gero Lindenblatt, MD, Katinka Fischer, MSc, Anna Gahlen, MD, Giovanni Novi, MD, Helen Hayward-Könnecke, MD, Sven Schippling, MD, Paulus S. Rommer, MD, Barbara Kornek, MD, Tobias Zrzavy, MD, Damien Biotti, MD, Jonathan Ciron, MD, Bertrand Audoin, MD, Achim Berthele, MD, Katrin Giglhuber, MD, Helene Zephir, MD, Tania Kümpfel, MD, Robert Berger, MD, Joachim Röther, MD, Vivien Häußler, MD, Jan-Patrick Stellmann, MD, Daniel Whittam, MD, Anu Jacob, MD, Markus Kraemer, MD, Antoine Gueguen, MD, Romain Deschamps, MD, Antonios Bayas, MD, Martin W. Hümmert, MD, Corinna Trebst, MD, Axel Haarmann, MD, Sven Jarius, MD, Brigitte Wildemann, MD, Matthias Grothe, MD, Nadja Siebert, MD, Klemens Ruprecht, MD, Friedemann Paul, MD, Nicolas Collongues, MD, Romain Marignier, MD, Michael Levy, MD, Michael Karenfort, MD, Michael Deppe, PhD, Philipp Albrecht, MD, Kerstin Hellwig, MD, Ralf Gold, MD, Hans-Peter Hartung, MD, Sven G. Meuth, MD, Ingo Kleiter, MD, Orhan Aktas, MD, on behalf of the Neuromyelitis Optica Study Group (NEMOS) 
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520 |a 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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700 1 |a Schippling, Sven  |e VerfasserIn  |4 aut 
700 1 |a Rommer, Paulus S.  |e VerfasserIn  |4 aut 
700 1 |a Kornek, Barbara  |e VerfasserIn  |4 aut 
700 1 |a Zrzavy, Tobias  |e VerfasserIn  |4 aut 
700 1 |a Biotti, Damien  |e VerfasserIn  |4 aut 
700 1 |a Ciron, Jonathan  |e VerfasserIn  |4 aut 
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