Itay Lotan1, Robert W Charlson2, Lana Zhovtis Ryerson2, Michael Levy3, Ilya Kister2. 1. New York University Langone Medical Center, Multiple Sclerosis Comprehensive Care Center, New York, USA; Department of Neurology and Neuroimmunology Unit, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: itay.lotan@nyulangone.org. 2. New York University Langone Medical Center, Multiple Sclerosis Comprehensive Care Center, New York, USA. 3. Division of Neuroimmunology and Neuroinfectious Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
Abstract
BACKGROUND: Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 receptor, is approved for treatment of rheumatoid arthritis and several other immune-mediated disorders. Off-label use of the intravenous formulation of tocilizumab for Neuromyelitis Optica Spectrum Disorder (NMOSD) decreased relapse rates in two small case series. However, treatment protocol that requires frequent intravenous infusions may adversely affect adherence to therapy, especially in the more disabled patients, thereby reducing effectiveness. A subcutaneous formulation of tocilizumab was shown to be noninferior to the IV formulation for approved rheumatologic diseases. The effectiveness of subcutaneous TCZ for NMOSD is unknown. METHODS: We retrospectively reviewed clinical, radiological and serological data on all NMOSD patients who received subcutaneous TCZ in two tertiary referral centers between 2014-2019. RESULTS: Twelve NMOSD patients who received at least 6 months of subcutaneous TCZ were identified. Eleven were female; mean age was 46.9 ± 14.5 years and mean disease duration was 6.6 ± 4.6 years. Seven patients were seropositive for AQP-4 antibodies, two - for MOG-IgG antibodies, and three were doubly seronegative. During subcutaneous TCZ treatment, eight patients (66.6%) were relapse-free, one patient (8.3%) experienced 1 relapse, two patients (16.6%) - 2 relapses, and one patient (8.3%) - 3 relapses. The median relapse rate within 1 year after starting subcutaneous TCZ - 0 (interquartile range =1.75-0) - was significantly lower than in the year prior to treatment initiation (2, interquartile range = 4.0-0.25; p = 0.04). Overall, the annual relapse rate (ARR) decreased from a median of 2 (interquartile range = 5.75-1.29) prior to subcutaneous TCZ to 0 (interquartile range= = 1.0-0) on treatment (p = 0.0015). One TCZ-treated patient died following a severe myelitis attack. CONCLUSIONS: Effectiveness of subcutaneous TCZ in NMOSD appears to be similar to that reported for the IV formulation and has an advantage of at-home administration. Prospective, comparative studies of subcutaneous TCZ for NMOSD are warranted.
BACKGROUND: Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 receptor, is approved for treatment of rheumatoid arthritis and several other immune-mediated disorders. Off-label use of the intravenous formulation of tocilizumab for Neuromyelitis Optica Spectrum Disorder (NMOSD) decreased relapse rates in two small case series. However, treatment protocol that requires frequent intravenous infusions may adversely affect adherence to therapy, especially in the more disabled patients, thereby reducing effectiveness. A subcutaneous formulation of tocilizumab was shown to be noninferior to the IV formulation for approved rheumatologic diseases. The effectiveness of subcutaneous TCZ for NMOSD is unknown. METHODS: We retrospectively reviewed clinical, radiological and serological data on all NMOSDpatients who received subcutaneous TCZ in two tertiary referral centers between 2014-2019. RESULTS: Twelve NMOSDpatients who received at least 6 months of subcutaneous TCZ were identified. Eleven were female; mean age was 46.9 ± 14.5 years and mean disease duration was 6.6 ± 4.6 years. Seven patients were seropositive for AQP-4 antibodies, two - for MOG-IgG antibodies, and three were doubly seronegative. During subcutaneous TCZ treatment, eight patients (66.6%) were relapse-free, one patient (8.3%) experienced 1 relapse, two patients (16.6%) - 2 relapses, and one patient (8.3%) - 3 relapses. The median relapse rate within 1 year after starting subcutaneous TCZ - 0 (interquartile range =1.75-0) - was significantly lower than in the year prior to treatment initiation (2, interquartile range = 4.0-0.25; p = 0.04). Overall, the annual relapse rate (ARR) decreased from a median of 2 (interquartile range = 5.75-1.29) prior to subcutaneous TCZ to 0 (interquartile range= = 1.0-0) on treatment (p = 0.0015). One TCZ-treated patient died following a severe myelitis attack. CONCLUSIONS: Effectiveness of subcutaneous TCZ in NMOSD appears to be similar to that reported for the IV formulation and has an advantage of at-home administration. Prospective, comparative studies of subcutaneous TCZ for NMOSD are warranted.
Authors: Marius Ringelstein; Ilya Ayzenberg; Gero Lindenblatt; Katinka Fischer; Anna Gahlen; Giovanni Novi; Helen Hayward-Könnecke; Sven Schippling; Paulus S Rommer; Barbara Kornek; Tobias Zrzavy; Damien Biotti; Jonathan Ciron; Bertrand Audoin; Achim Berthele; Katrin Giglhuber; Helene Zephir; Tania Kümpfel; Robert Berger; Joachim Röther; Vivien Häußler; Jan-Patrick Stellmann; Daniel Whittam; Anu Jacob; Markus Kraemer; Antoine Gueguen; Romain Deschamps; Antonios Bayas; Martin W Hümmert; Corinna Trebst; Axel Haarmann; Sven Jarius; Brigitte Wildemann; Matthias Grothe; Nadja Siebert; Klemens Ruprecht; Friedemann Paul; Nicolas Collongues; Romain Marignier; Michael Levy; Michael Karenfort; Michael Deppe; Philipp Albrecht; Kerstin Hellwig; Ralf Gold; Hans-Peter Hartung; Sven G Meuth; Ingo Kleiter; Orhan Aktas Journal: Neurol Neuroimmunol Neuroinflamm Date: 2021-11-16