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

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Item Type:Article
Title:Interleukin-6 receptor blockade in treatment-refractory MOG-IgG-associated disease and neuromyelitis optica spectrum disorders
Creators Name:Ringelstein, M. and Ayzenberg, I. and Lindenblatt, G. and Fischer, K. and Gahlen, A. and Novi, G. and Hayward-Könnecke, H. and Schippling, S. and Rommer, P.S. and Kornek, B. and Zrzavy, T. and Biotti, D. and Ciron, J. and Audoin, B. and Berthele, A. and Giglhuber, K. and Zephir, H. and Kümpfel, T. and Berger, R. and Röther, J. and Häußler, V. and Stellmann, J.P. and Whittam, D. and Jacob, A. and Kraemer, M. and Gueguen, A. and Deschamps, R. and Bayas, A. and Hümmert, M.W. and Trebst, C. and Haarmann, A. and Jarius, S. and Wildemann, B. and Grothe, M. and Siebert, N. and Ruprecht, K. and Paul, F. and Collongues, N. and Marignier, R. and Levy, M. and Karenfort, M. and Deppe, M. and Albrecht, P. and Hellwig, K. and Gold, R. and Hartung, H.P. and Meuth, S.G. and Kleiter, I. and Aktas, O.
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.
Source:Neurology Neuroimmunology & Neuroinflammation
ISSN:2332-7812
Publisher:American Academy of Neurology
Volume:9
Number:1
Page Range:e1100
Date:January 2022
Official Publication:https://doi.org/10.1212/NXI.0000000000001100
PubMed:View item in PubMed

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