Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab, and Eculizumab in NMOSD

Summary

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare autoimmune condition that mainly affects the eyes and spinal cord, causing serious symptoms such as vision loss, paralysis, and severe pain. This trial compares the effectiveness and safety of five medications commonly used to prevent NMOSD relapses: rituximab, ravulizumab, inebilizumab, satralizumab, and eculizumab. In this study, 160 adults with NMOSD who test positive for a specific antibody (AQP4-IgG) will participate. They will be randomly assigned to receive either rituximab or one of the four other FDA-approved medications. The main goal is to find out which treatment best prevents relapses and has fewer serious side effects. The trial will also measure disability, patient satisfaction, quality of life, and biomarkers that help track disease activity. Participants will have regular assessments, including medical exams, surveys, and tests for vision, walking ability, and brain function. They will report any side effects or health issues experienced during the study. The trial will last from one to four years for each participant. This research aims to help patients and doctors make better-informed treatment decisions by providing clear evidence about the best available therapies for NMOSD.

Timeline

Start

2026-08-01

Primary completion

2030-01

Completion

2030-05

Publications

• Background Barreras P, Vasileiou ES, Filippatou AG, Fitzgerald KC, Levy M, Pardo CA, Newsome SD, Mowry EM, Calabresi PA, Sotirchos ES. Long-term Effectiveness and Safety of Rituximab in Neuromyelitis Optica Spectrum Disorder and MOG Antibody Disease. Neurology. 2022 Nov 29;99(22):e2504-e2516. doi: 10.1212/WNL.0000000000201260. Epub 2022 Aug 31.
• Background Yamamura T, Weinshenker B, Yeaman MR, De Seze J, Patti F, Lobo P, von Budingen HC, Kou X, Weber K, Greenberg B. Long-term safety of satralizumab in neuromyelitis optica spectrum disorder (NMOSD) from SAkuraSky and SAkuraStar. Mult Scler Relat Disord. 2022 Oct;66:104025. doi: 10.1016/j.msard.2022.104025. Epub 2022 Jul 5.
• Background Rensel M, Zabeti A, Mealy MA, Cimbora D, She D, Drappa J, Katz E. Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: Analysis of aquaporin-4-immunoglobulin G-seropositive participants taking inebilizumab for ⩾4 years in the N-MOmentum trial. Mult Scler. 2022 May;28(6):925-932. doi: 10.1177/13524585211047223. Epub 2021 Oct 1.
• Background Kumpfel T, Giglhuber K, Aktas O, Ayzenberg I, Bellmann-Strobl J, Haussler V, Havla J, Hellwig K, Hummert MW, Jarius S, Kleiter I, Klotz L, Krumbholz M, Paul F, Ringelstein M, Ruprecht K, Senel M, Stellmann JP, Bergh FT, Trebst C, Tumani H, Warnke C, Wildemann B, Berthele A; Neuromyelitis Optica Study Group (NEMOS). Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management. J Neurol. 2024 Jan;271(1):141-176. doi: 10.1007/s00415-023-11910-z. Epub 2023 Sep 7.
• Background Nosadini M, Alper G, Riney CJ, Benson LA, Mohammad SS, Ramanathan S, Nolan M, Appleton R, Leventer RJ, Deiva K, Brilot F, Gorman MP, Waldman AT, Banwell B, Dale RC. Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2016 Jan 21;3(1):e188. doi: 10.1212/NXI.0000000000000188. eCollection 2016 Feb.
• Background Rover C, Friede T. Dynamically borrowing strength from another study through shrinkage estimation. Stat Methods Med Res. 2020 Jan;29(1):293-308. doi: 10.1177/0962280219833079. Epub 2019 Mar 1.
• Background Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015 Jul 14;85(2):177-89. doi: 10.1212/WNL.0000000000001729. Epub 2015 Jun 19.
• Background Marcinno A, Marnetto F, Valentino P, Martire S, Balbo A, Drago A, Leto M, Capobianco M, Panzica G, Bertolotto A. Rituximab-induced hypogammaglobulinemia in patients with neuromyelitis optica spectrum disorders. Neurol Neuroimmunol Neuroinflamm. 2018 Sep 13;5(6):e498. doi: 10.1212/NXI.0000000000000498. eCollection 2018 Nov.
• Background Clardy SL, Pittock SJ, Aktas O, Nakahara J, Isobe N, Centonze D, Fam S, Kielhorn A, Yu JC, Jansen J, Zhang I. Network Meta-analysis of Ravulizumab and Alternative Interventions for the Treatment of Neuromyelitis Optica Spectrum Disorder. Neurol Ther. 2024 Jun;13(3):535-549. doi: 10.1007/s40120-024-00597-7. Epub 2024 May 9.
• Background Yamamura T, Kleiter I, Fujihara K, Palace J, Greenberg B, Zakrzewska-Pniewska B, Patti F, Tsai CP, Saiz A, Yamazaki H, Kawata Y, Wright P, De Seze J. Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 Nov 28;381(22):2114-2124. doi: 10.1056/NEJMoa1901747.
• Background Pittock SJ, Barnett M, Bennett JL, Berthele A, de Seze J, Levy M, Nakashima I, Oreja-Guevara C, Palace J, Paul F, Pozzilli C, Yountz M, Allen K, Mashhoon Y, Kim HJ. Ravulizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. Ann Neurol. 2023 Jun;93(6):1053-1068. doi: 10.1002/ana.26626. Epub 2023 Apr 5.
• Background Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J, Nakashima I, Terzi M, Totolyan N, Viswanathan S, Wang KC, Pace A, Fujita KP, Armstrong R, Wingerchuk DM. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 Aug 15;381(7):614-625. doi: 10.1056/NEJMoa1900866. Epub 2019 May 3.
• Background Tahara M, Oeda T, Okada K, Kiriyama T, Ochi K, Maruyama H, Fukaura H, Nomura K, Shimizu Y, Mori M, Nakashima I, Misu T, Umemura A, Yamamoto K, Sawada H. Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2020 Apr;19(4):298-306. doi: 10.1016/S1474-4422(20)30066-1. Epub 2020 Mar 18.
• Background Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013 Sep 1;70(9):1110-7. doi: 10.1001/jamaneurol.2013.3071.
• Background Kleiter I, Gold R. Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders. Neurotherapeutics. 2016 Jan;13(1):70-83. doi: 10.1007/s13311-015-0400-8.
• Background Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, Borisow N, Kleiter I, Aktas O, Kumpfel T; Neuromyelitis Optica Study Group (NEMOS). Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol. 2014 Jan;261(1):1-16. doi: 10.1007/s00415-013-7169-7. Epub 2013 Nov 23.
• Background Sellner J, Boggild M, Clanet M, Hintzen RQ, Illes Z, Montalban X, Du Pasquier RA, Polman CH, Sorensen PS, Hemmer B. EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol. 2010 Aug;17(8):1019-32. doi: 10.1111/j.1468-1331.2010.03066.x. Epub 2010 Jun 7.
• Background Mealy MA, Kessler RA, Rimler Z, Reid A, Totonis L, Cutter G, Kister I, Levy M. Mortality in neuromyelitis optica is strongly associated with African ancestry. Neurol Neuroimmunol Neuroinflamm. 2018 Jun 7;5(4):e468. doi: 10.1212/NXI.0000000000000468. eCollection 2018 Jul. No abstract available.
• Background Kim SH, Mealy MA, Levy M, Schmidt F, Ruprecht K, Paul F, Ringelstein M, Aktas O, Hartung HP, Asgari N, Tsz-Ching JL, Siritho S, Prayoonwiwat N, Shin HJ, Hyun JW, Han M, Leite MI, Palace J, Kim HJ. Racial differences in neuromyelitis optica spectrum disorder. Neurology. 2018 Nov 27;91(22):e2089-e2099. doi: 10.1212/WNL.0000000000006574. Epub 2018 Oct 26.
• Background Duchow A, Bellmann-Strobl J, Friede T, Aktas O, Angstwurm K, Ayzenberg I, Berthele A, Dawin E, Engels D, Fischer K, Flaskamp M, Giglhuber K, Grothe M, Havla J, Hummert MW, Jarius S, Kaste M, Kern P, Kleiter I, Klotz L, Korporal-Kuhnke M, Kraemer M, Krumbholz M, Kumpfel T, Lohmann L, Ringelstein M, Rommer P, Schindler P, Schubert C, Schwake C, Senel M, Then Bergh F, Tkachenko D, Tumani H, Trebst C, Vardakas I, Walter A, Warnke C, Weber MS, Wickel J, Wildemann B, Winkelmann A, Paul F, Stellmann JP, Haussler V; Neuromyelitis Optica Study Group (NEMOS). Time to Disability Milestones and Annualized Relapse Rates in NMOSD and MOGAD. Ann Neurol. 2024 Apr;95(4):720-732. doi: 10.1002/ana.26858. Epub 2024 Jan 13.
• Background Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Wegner B, Hellwig K, Pache F, Ruprecht K, Havla J, Krumbholz M, Kumpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Stellmann JP, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker R, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Winkelmann A, Marouf W, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C; Neuromyelitis Optica Study Group. Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol. 2016 Feb;79(2):206-16. doi: 10.1002/ana.24554. Epub 2015 Nov 26.
• Background O'Connell K, Hamilton-Shield A, Woodhall M, Messina S, Mariano R, Waters P, Ramdas S, Leite MI, Palace J. Prevalence and incidence of neuromyelitis optica spectrum disorder, aquaporin-4 antibody-positive NMOSD and MOG antibody-positive disease in Oxfordshire, UK. J Neurol Neurosurg Psychiatry. 2020 Oct;91(10):1126-1128. doi: 10.1136/jnnp-2020-323158. Epub 2020 Jun 23. No abstract available.
• Background Briggs FB, Shaia J. Prevalence of neuromyelitis optica spectrum disorder in the United States. Mult Scler. 2024 Jan 27:13524585231224683. doi: 10.1177/13524585231224683. Online ahead of print.
• Background Kitley J, Leite MI, Nakashima I, Waters P, McNeillis B, Brown R, Takai Y, Takahashi T, Misu T, Elsone L, Woodhall M, George J, Boggild M, Vincent A, Jacob A, Fujihara K, Palace J. Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain. 2012 Jun;135(Pt 6):1834-49. doi: 10.1093/brain/aws109. Epub 2012 May 9.
• Background Haussler V, Trebst C, Engels D, Pellkofer H, Havla J, Duchow A, Schindler P, Schwake C, Pakeerathan T, Fischer K, Ringelstein M, Lindenblatt G, Hummert MW, Tkachenko D, Butow F, Giglhuber K, Flaskamp M, Schiffmann I, Korporal-Kuhnke M, Jarius S, Dawin E, Revie L, Senel M, Herfurth M, Walter A, Pompsch M, Kleiter I, Angstwurm K, Kaste M, Grothe M, Wickel J, Rommer PS, Sieb JP, Kramer M, Then Bergh F, Tumani H, Klotz L, Wildemann B, Aktas O, Ayzenberg I, Bellmann-Strobl J, Paul F, Kumpfel T, Friede T, Berthele A, Stellmann JP; Neuromyelitis optica study group (NEMOS). Real-world multicentre cohort study on choices and effectiveness of immunotherapies in NMOSD and MOGAD. J Neurol Neurosurg Psychiatry. 2025 May 14;96(6):582-592. doi: 10.1136/jnnp-2024-334764.

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