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

Authors

  • M. Ringelstein
  • I. Ayzenberg
  • G. Lindenblatt
  • K. Fischer
  • A. Gahlen
  • G. Novi
  • H. Hayward-Könnecke
  • S. Schippling
  • P.S. Rommer
  • B. Kornek
  • T. Zrzavy
  • D. Biotti
  • J. Ciron
  • B. Audoin
  • A. Berthele
  • K. Giglhuber
  • H. Zephir
  • T. Kümpfel
  • R. Berger
  • J. Röther
  • V. Häußler
  • J.P. Stellmann
  • D. Whittam
  • A. Jacob
  • M. Kraemer
  • A. Gueguen
  • R. Deschamps
  • A. Bayas
  • M.W. Hümmert
  • C. Trebst
  • A. Haarmann
  • S. Jarius
  • B. Wildemann
  • M. Grothe
  • N. Siebert
  • K. Ruprecht
  • F. Paul
  • N. Collongues
  • R. Marignier
  • M. Levy
  • M. Karenfort
  • M. Deppe
  • P. Albrecht
  • K. Hellwig
  • R. Gold
  • H.P. Hartung
  • S.G. Meuth
  • I. Kleiter
  • O. Aktas

Journal

  • Neurology Neuroimmunology & Neuroinflammation

Citation

  • Neurol Neuroimmunol Neuroinflamm 9 (1): e1100

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.


DOI

doi:10.1212/NXI.0000000000001100