RT Journal Article
SR Electronic
T1 Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG–Associated Disease and Neuromyelitis Optica Spectrum Disorders
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e1100
DO 10.1212/NXI.0000000000001100
VO 9
IS 1
A1 Ringelstein, Marius
A1 Ayzenberg, Ilya
A1 Lindenblatt, Gero
A1 Fischer, Katinka
A1 Gahlen, Anna
A1 Novi, Giovanni
A1 Hayward-Könnecke, Helen
A1 Schippling, Sven
A1 Rommer, Paulus S.
A1 Kornek, Barbara
A1 Zrzavy, Tobias
A1 Biotti, Damien
A1 Ciron, Jonathan
A1 Audoin, Bertrand
A1 Berthele, Achim
A1 Giglhuber, Katrin
A1 Zephir, Helene
A1 Kümpfel, Tania
A1 Berger, Robert
A1 Röther, Joachim
A1 Häußler, Vivien
A1 Stellmann, Jan-Patrick
A1 Whittam, Daniel
A1 Jacob, Anu
A1 Kraemer, Markus
A1 Gueguen, Antoine
A1 Deschamps, Romain
A1 Bayas, Antonios
A1 Hümmert, Martin W.
A1 Trebst, Corinna
A1 Haarmann, Axel
A1 Jarius, Sven
A1 Wildemann, Brigitte
A1 Grothe, Matthias
A1 Siebert, Nadja
A1 Ruprecht, Klemens
A1 Paul, Friedemann
A1 Collongues, Nicolas
A1 Marignier, Romain
A1 Levy, Michael
A1 Karenfort, Michael
A1 Deppe, Michael
A1 Albrecht, Philipp
A1 Hellwig, Kerstin
A1 Gold, Ralf
A1 Hartung, Hans-Peter
A1 Meuth, Sven G.
A1 Kleiter, Ingo
A1 Aktas, Orhan
A1 ,
YR 2022
UL http://nn.neurology.org/content/9/1/e1100.abstract
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