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

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Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders. / Ringelstein, Marius; Ayzenberg, Ilya; Lindenblatt, Gero; Fischer, Katinka; Gahlen, Anna; Novi, Giovanni; Hayward-Könnecke, Helen; Schippling, Sven; Rommer, Paulus S; Kornek, Barbara; Zrzavy, Tobias; Biotti, Damien; Ciron, Jonathan; Audoin, Bertrand; Berthele, Achim; Giglhuber, Katrin; Zephir, Helene; Kümpfel, Tania; Berger, Robert; Röther, Joachim; Häußler, Vivien; Stellmann, Jan-Patrick; Whittam, Daniel; Jacob, Anu; Kraemer, Markus; Gueguen, Antoine; Deschamps, Romain; Bayas, Antonios; Hümmert, Martin W; Trebst, Corinna; Haarmann, Axel; Jarius, Sven; Wildemann, Brigitte; Grothe, Matthias; Siebert, Nadja; Ruprecht, Klemens; Paul, Friedemann; Collongues, Nicolas; Marignier, Romain; Levy, Michael; Karenfort, Michael; Deppe, Michael; Albrecht, Philipp; Hellwig, Kerstin; Gold, Ralf; Hartung, Hans-Peter; Meuth, Sven G; Kleiter, Ingo; Aktas, Orhan; Neuromyelitis Optica Study Group (NEMOS).

In: NEUROL-NEUROIMMUNOL, Vol. 9, No. 1, e1100, 01.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Ringelstein, M, Ayzenberg, I, Lindenblatt, G, Fischer, K, Gahlen, A, Novi, G, Hayward-Könnecke, H, Schippling, S, Rommer, PS, Kornek, B, Zrzavy, T, Biotti, D, Ciron, J, Audoin, B, Berthele, A, Giglhuber, K, Zephir, H, Kümpfel, T, Berger, R, Röther, J, Häußler, V, Stellmann, J-P, Whittam, D, Jacob, A, Kraemer, M, Gueguen, A, Deschamps, R, Bayas, A, Hümmert, MW, Trebst, C, Haarmann, A, Jarius, S, Wildemann, B, Grothe, M, Siebert, N, Ruprecht, K, Paul, F, Collongues, N, Marignier, R, Levy, M, Karenfort, M, Deppe, M, Albrecht, P, Hellwig, K, Gold, R, Hartung, H-P, Meuth, SG, Kleiter, I, Aktas, O & Neuromyelitis Optica Study Group (NEMOS) 2022, 'Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders', NEUROL-NEUROIMMUNOL, vol. 9, no. 1, e1100. https://doi.org/10.1212/NXI.0000000000001100

APA

Ringelstein, M., Ayzenberg, I., Lindenblatt, G., Fischer, K., Gahlen, A., Novi, G., Hayward-Könnecke, H., Schippling, S., Rommer, P. S., Kornek, B., Zrzavy, T., Biotti, D., Ciron, J., Audoin, B., Berthele, A., Giglhuber, K., Zephir, H., Kümpfel, T., Berger, R., ... Neuromyelitis Optica Study Group (NEMOS) (2022). Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders. NEUROL-NEUROIMMUNOL, 9(1), [e1100]. https://doi.org/10.1212/NXI.0000000000001100

Vancouver

Ringelstein M, Ayzenberg I, Lindenblatt G, Fischer K, Gahlen A, Novi G et al. Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders. NEUROL-NEUROIMMUNOL. 2022 Jan;9(1). e1100. https://doi.org/10.1212/NXI.0000000000001100

Bibtex

@article{4603022572a342349e261d46fe071813,
title = "Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders",
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.",
author = "Marius Ringelstein and Ilya Ayzenberg and Gero Lindenblatt and Katinka Fischer and Anna Gahlen and Giovanni Novi and Helen Hayward-K{\"o}nnecke and Sven Schippling and Rommer, {Paulus S} and Barbara Kornek and Tobias Zrzavy and Damien Biotti and Jonathan Ciron and Bertrand Audoin and Achim Berthele and Katrin Giglhuber and Helene Zephir and Tania K{\"u}mpfel and Robert Berger and Joachim R{\"o}ther and Vivien H{\"a}u{\ss}ler and Jan-Patrick Stellmann and Daniel Whittam and Anu Jacob and Markus Kraemer and Antoine Gueguen and Romain Deschamps and Antonios Bayas and H{\"u}mmert, {Martin W} and Corinna Trebst and Axel Haarmann and Sven Jarius and Brigitte Wildemann and Matthias Grothe and Nadja Siebert and Klemens Ruprecht and Friedemann Paul and Nicolas Collongues and Romain Marignier and Michael Levy and Michael Karenfort and Michael Deppe and Philipp Albrecht and Kerstin Hellwig and Ralf Gold and Hans-Peter Hartung and Meuth, {Sven G} and Ingo Kleiter and Orhan Aktas and {Neuromyelitis Optica Study Group (NEMOS)}",
note = "Copyright {\textcopyright} 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.",
year = "2022",
month = jan,
doi = "10.1212/NXI.0000000000001100",
language = "English",
volume = "9",
journal = "NEUROL-NEUROIMMUNOL",
issn = "2332-7812",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

RIS

TY - JOUR

T1 - Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders

AU - Ringelstein, Marius

AU - Ayzenberg, Ilya

AU - Lindenblatt, Gero

AU - Fischer, Katinka

AU - Gahlen, Anna

AU - Novi, Giovanni

AU - Hayward-Könnecke, Helen

AU - Schippling, Sven

AU - Rommer, Paulus S

AU - Kornek, Barbara

AU - Zrzavy, Tobias

AU - Biotti, Damien

AU - Ciron, Jonathan

AU - Audoin, Bertrand

AU - Berthele, Achim

AU - Giglhuber, Katrin

AU - Zephir, Helene

AU - Kümpfel, Tania

AU - Berger, Robert

AU - Röther, Joachim

AU - Häußler, Vivien

AU - Stellmann, Jan-Patrick

AU - Whittam, Daniel

AU - Jacob, Anu

AU - Kraemer, Markus

AU - Gueguen, Antoine

AU - Deschamps, Romain

AU - Bayas, Antonios

AU - Hümmert, Martin W

AU - Trebst, Corinna

AU - Haarmann, Axel

AU - Jarius, Sven

AU - Wildemann, Brigitte

AU - Grothe, Matthias

AU - Siebert, Nadja

AU - Ruprecht, Klemens

AU - Paul, Friedemann

AU - Collongues, Nicolas

AU - Marignier, Romain

AU - Levy, Michael

AU - Karenfort, Michael

AU - Deppe, Michael

AU - Albrecht, Philipp

AU - Hellwig, Kerstin

AU - Gold, Ralf

AU - Hartung, Hans-Peter

AU - Meuth, Sven G

AU - Kleiter, Ingo

AU - Aktas, Orhan

AU - Neuromyelitis Optica Study Group (NEMOS)

N1 - Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

U2 - 10.1212/NXI.0000000000001100

DO - 10.1212/NXI.0000000000001100

M3 - SCORING: Journal article

C2 - 34785575

VL - 9

JO - NEUROL-NEUROIMMUNOL

JF - NEUROL-NEUROIMMUNOL

SN - 2332-7812

IS - 1

M1 - e1100

ER -