PT  - JOURNAL ARTICLE
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  - on behalf of the Neuromyelitis Optica Study Group (NEMOS)
TI  - Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG–Associated Disease and Neuromyelitis Optica Spectrum Disorders
AID  - 10.1212/NXI.0000000000001100
DP  - 2022 Jan 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e1100
VI  - 9
IP  - 1
4099  - http://nn.neurology.org/content/9/1/e1100.short
4100  - http://nn.neurology.org/content/9/1/e1100.full
SO  - Neurol Neuroimmunol Neuroinflamm2022 Jan 01; 9
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.ADEM=acute disseminated encephalomyelitis; AQP4=aquaporin-4; ARR=annualized relapse rate; AZA=azathioprine; EDSS=Expanded Disability Status Scale; HDS=high-dose steroid; IL-6=interleukin-6; IQR=interquartile range; IVIG=IV immunoglobulin; LDS=low-dose steroid; MMF=mycophenolate mofetil; MOG=myelin oligodendrocyte glycoprotein; MOGAD=myelin oligodendrocyte glycoprotein–IgG–associated disease; MTX=methotrexate; NMOSD=neuromyelitis optica spectrum disorder; ON=optic neuritis; RTX=rituximab; SLE=systemic lupus erythematosus; TCZ=tocilizumab; UTI=urinary tract infection