BRAIN and NERVE－神経研究の進歩76巻10号

2024年10月発行

総説

視神経脊髄炎スペクトラム障害治療におけるCD19モノクローナル抗体製剤イネビリズマブの有効性および安全性—N-MOmentum試験を中心に

著者： 藤原一男¹² 佐藤裕一³

所属機関： ¹福島県立医科大学医学部多発性硬化症治療学講座 ²一般財団法人脳神経疾患研究所多発性硬化症・視神経脊髄炎センター ³田辺三菱製薬株式会社開発・メディカル本部メディカルアフェアーズ

ページ範囲：P.1153 - P.1160

文献概要

視神経脊髄炎スペクトラム障害（neuromyelitis optica spectrum disorders：NMOSD）は視神経炎と横断性脊髄炎を特徴とする炎症性中枢神経疾患である。イネビリズマブはCD19に対するヒト化IgG1モノクローナル抗体であり，日本人も参加した国際共同二重盲検プラセボ対照第Ⅱ/Ⅲ相試験のN-MOmentum試験でNMOSD患者に対する有効性と安全性が検証され，わが国でも製造販売承認された。本論文では，N-MOmentum試験およびその追加解析で得られたイネビリズマブの有効性および安全性の知見を解説する。

参考文献

1）Fujihara K, Misu T, Nakashima I, Takahashi T, Bradl M, et al: Neuromyelitis optica should be classified as an astrocytopathic disease rather than a demyelinating disease. Clin Exp Neuroimmunol 3: 58-73, 2012

2）Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, et al; International Panel for NMO Diagnosis: International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85: 177-189, 2015

3）糸谷拓也, 松本勇貴, 藤原一男: 視神経脊髄炎スペクトラム障害. Prog Med 41: 131-134, 2021

4）福與なおみ, 藤原一男: 小児の中枢神経系脱髄性疾患（急性散在性脳脊髄炎, 多発性硬化症）の眼症状. あたらしい眼科38: 1035-1041, 2021

5）清水優子, 藤原一男: 多発性硬化症，視神経脊髄炎. Clin Neurosci 39: 99-102, 2021

6）日本神経学会（監修）, 「多発性硬化症・視神経脊髄炎スペクトラム 障害診療ガイドライン」作成委員会（編）: 多発性硬化症・視神経脊髄炎スペクトラム障害診療ガイドライン2023. 医学書院, 東京, 2023

7）Kimbrough DJ, Fujihara K, Jacob A, Lana-Peixoto MA, Leite MI, et al; GJCF-CC＆BR: Treatment of neuromyelitis optica: review and recommendations. Mult Scler Relat Disord 1: 180-187, 2012

8）Forsthuber TG, Cimbora DM, Ratchford JN, Katz E, Stüve O: B cell-based therapies in CNS autoimmunity: differentiating CD19 and CD20 as therapeutic targets. Ther Adv Neurol Disord 11: 1756286418761697, 2018［doi: 10.1177/1756286418761697］

9）Yong HYF, Burton JM: A Clinical Approach to Existing and Emerging Therapeutics in Neuromyelitis Optica Spectrum Disorder. Curr Neurol Neurosci Rep 23: 489-506, 2023

10）Cree BAC, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, et al; N-MOmentum study investigators: Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet 394: 1352-1363, 2019

11）田辺三菱製薬株式会社: ユプリズナ®点滴静注100mg添付文書. 第1版: 2021年3月作成

12）Paul F, Marignier R, Palace J, Arrambide G, Asgari N, et al: International Delphi Consensus on the Management of AQP4-IgG＋ NMOSD: Recommendations for Eculizumab, Inebilizumab, and Satralizumab. Neurol Neuroimmunol Neuroinflamm 10: e200124, 2023［doi: 10.1212/NXI.0000000000200124］

13）Cree BAC, Greenberg B, Cameron C, Weinshenker BG: Letter to the Editor Regarding “Network Meta-analysis of Food and Drug Administration-approved Treatment Options for Adults with Aquaporin-4 Immunoglobulin G-positive Neuromyelitis Optica Spectrum Disorder”. Neurol Ther 11: 1439-1443, 2022

14）Cree BA, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, et al: Sensitivity analysis of the primary endpoint from the N-MOmentum study of inebilizumab in NMOSD. Mult Scler 27: 2052-2061, 2021

15）Weinshenker BG, Wingerchuk DM, Green AJ, Bennett JL, Kim HJ, et al: Attack adjudication in neuromyelitis optica spectrum disorder: Substantiation of criteria by magnetic resonance imaging and biomarkers in N-MOmentum. Mult Scler 29: 945-955, 2023

16）Aktas O, Smith MA, Rees WA, Bennett JL, She D, et al; N-MOmentum scientific group and the N-MOmentum study investigators: Serum Glial Fibrillary Acidic Protein: A Neuromyelitis Optica Spectrum Disorder Biomarker. Ann Neurol 89: 895-910, 2021

17）Aktas O, Hartung HP, Smith MA, Rees WA, Fujihara K, et al; N-MOmentum study investigators: Serum neurofilament light chain levels at attack predict post-attack disability worsening and are mitigated by inebilizumab: analysis of four potential biomarkers in neuromyelitis optica spectrum disorder. J Neurol Neurosurg Psychiatry 94: 757-768, 2023

18）Bennett JL, Aktas O, Rees WA, Smith MA, Gunsior M, et al; N-MOmentum study investigators: Association between B-cell depletion and attack risk in neuromyelitis optica spectrum disorder: An exploratory analysis from N-MOmentum, a double-blind, randomised, placebo-controlled, multicentre phase 2/3 trial. EBioMedicine 86: 104321, 2022［doi: 10.1016/j.ebiom.2022.104321］

19）Marignier R, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, et al; N-MOmentum Study Investigators: Disability Outcomes in the N-MOmentum Trial of Inebilizumab in Neuromyelitis Optica Spectrum Disorder. Neurol Neuroimmunol Neuroinflamm 8: e978, 2021［doi: 10.1212/NXI.0000000000000978］

20）Flanagan EP, Levy M, Katz E, Cimbora D, Drappa J, et al: Inebilizumab for treatment of neuromyelitis optica spectrum disorder in patients with prior rituximab use from the N-MOmentum Study. Mult Scler Relat Disord 57: 103352, 2022［doi: 10.1016/j.msard.2021.103352］

21）Kim SH, Jeong IH, Hyun JW, Joung A, Jo HJ, et al: Treatment outcomes with rituximab in 100 patients with neuromyelitis optica: influence of FCGR3A polymorphisms on the therapeutic response to rituximab. JAMA Neurol 72: 989-995, 2015

22）Kim HJ, Aktas O, Patterson KR, Korff S, Kunchok A, et al: Inebilizumab reduces neuromyelitis optica spectrum disorder risk independent of FCGR3A polymorphism. Ann Clin Transl Neurol 10: 2413-2420, 2023

23）Fujihara K, Kim HJ, Saida T, Misu T, Nagano Y, et al: Efficacy and safety of inebilizumab in Asian participants with neuromyelitis optica spectrum disorder: Subgroup analyses of the N-MOmentum study. Mult Scler Relat Disord 79: 104938, 2023［doi: 10.1016/j.msard.2023.104938］

24）Rensel M, Zabeti A, Mealy MA, Cimbora D, She D, et al: 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 28: 925-932, 2022

25）Kim SH, Park NY, Kim KH, Hyun JW, Kim HJ: Rituximab-Induced Hypogammaglobulinemia and Risk of Infection in Neuromyelitis Optica Spectrum Disorders: A 14-Year Real-Life Experience. Neurol Neuroimmunol Neuroinflamm 9: e1179, 2022［doi: 10.1212/NXI.0000000000001179］

26）Tieu J, Smith RM, Gopaluni S, Kumararatne DS, McClure M, et al: Rituximab Associated Hypogammaglobulinemia in Autoimmune Disease. Front Immunol 12: 671503, 2021［doi: 10.3389/fimmu.2021.671503］

27）Marco H, Smith RM, Jones RB, Guerry MJ, Catapano F, et al: The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease. BMC Musculoskelet Disord 15: 178, 2014［doi: 10.1186/1471-2474-15-178］

28）Liberatore J, Nguyen Y, Hadjadj J, Cohen P, Mouthon L, et al: Risk factors for hypogammaglobulinemia and association with relapse and severe infections in ANCA-associated vasculitis: A cohort study. J Autoimmun 142: 103130, 2024［doi: 10.1016/j.jaut.2023.103130］

29）Boleto G, Avouac J, Wipff J, Forien M, Dougados M, et al: Predictors of hypogammaglobulinemia during rituximab maintenance therapy in rheumatoid arthritis: A 12-year longitudinal multi-center study. Semin Arthritis Rheum 48: 149-154, 2018

30）Kawano T, Matsuse H, Obase Y, Kondo Y, Machida I, et al: Hypogammaglobulinemia in steroid-dependent asthmatics correlates with the daily dose of oral prednisolone. Int Arch Allergy Immunol 128: 240-243, 2002

31）Akaishi T, Nakashima I, Takahashi T, Abe M, Ishii T, et al: Neuromyelitis optica spectrum disorders with unevenly clustered attack occurrence. Neurol Neuroimmunol Neuroinflamm 7: e640, 2020［doi: 10.1212/NXI.0000000000000640］