N-MOmentum 试验中依那西普治疗视神经脊髓炎谱系疾病的残疾结局。

Disability Outcomes in the N-MOmentum Trial of Inebilizumab in Neuromyelitis Optica Spectrum Disorder.

机构信息

From the Service de Neurologie Sclérose en Plaques (R.M.), Pathologies de La Myéline et Neuro-inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, France; University of Colorado School of Medicine (J.L.B.), Anschutz Medical Campus, Aurora; Research Institute and Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; Mayo Clinic (B.G.W., S.J.P.), Rochester, MN; Mayo Clinic (D.W.), Scottsdale, AZ; Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University and Multiple Sclerosis and Neuromyelitis Optica Center, Southern Tohoku Research Institute for Neuroscience, Koriyama, Japan; Experimental and Clinical Research Center (F.P.), Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany; University of Alabama at Birmingham (G.R.C.); UCSF Weill Institute for Neurosciences (A.J.G.), Department of Neurology and Department of Ophthalmology, University of California San Francisco; Medical Faculty (O.A., H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Icahn School of Medicine at Mount Sinai (F.D.L.), New York; Oxford PharmaGenesis Ltd (I.M.W.), UK; Viela Bio (J.D., D.S., D.C., W.R., M.S., J.N.R., E.K.), Gaithersburg, MD; and UCSF Weill Institute for Neurosciences (B.A.C.C.), University of California San Francisco.

出版信息

Neurol Neuroimmunol Neuroinflamm. 2021 Mar 26;8(3). doi: 10.1212/NXI.0000000000000978. Print 2021 May.

DOI:10.1212/NXI.0000000000000978

PMID:33771837

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8054974/

Abstract

OBJECTIVE

To assess treatment effects on Expanded Disability Status Scale (EDSS) score worsening and modified Rankin Scale (mRS) scores in the N-MOmentum trial of inebilizumab, a humanized anti-CD19 monoclonal antibody, in participants with neuromyelitis optica spectrum disorder (NMOSD).

METHODS

Adults (N = 230) with aquaporin-4 immunoglobulin G-seropositive NMOSD or -seronegative neuromyelitis optica and an EDSS score ≤8 were randomized (3:1) to receive inebilizumab 300 mg or placebo on days 1 and 15. The randomized controlled period (RCP) was 28 weeks or until adjudicated attack, with an option to enter the inebilizumab open-label period. Three-month EDSS-confirmed disability progression (CDP) was assessed using a Cox proportional hazard model. The effect of baseline subgroups on disability was assessed by interaction tests. mRS scores from the RCP were analyzed by the Wilcoxon-Mann-Whitney odds approach.

RESULTS

Compared with placebo, inebilizumab reduced the risk of 3-month CDP (hazard ratio [HR]: 0.375; 95% CI: 0.148-0.952; = 0.0390). Baseline disability, prestudy attack frequency, and disease duration did not affect the treatment effect observed with inebilizumab (HRs: 0.213-0.503; interaction tests: all > 0.05, indicating no effect of baseline covariates on outcome). Mean EDSS scores improved with longer-term treatment. Inebilizumab-treated participants were more likely to have a favorable mRS outcome at the end of the RCP (OR: 1.663; 95% CI: 1.195-2.385; = 0.0023).

CONCLUSIONS

Disability outcomes were more favorable with inebilizumab vs placebo in participants with NMOSD.

CLASSIFICATION OF EVIDENCE

This study provides Class II evidence that for patients with NMOSD, inebilizumab reduces the risk of worsening disability. N-MOmentum is registered at ClinicalTrials.gov: NCT02200770.

摘要

目的

评估伊奈利珠单抗（一种人源化抗 CD19 单克隆抗体）在视神经脊髓炎谱系障碍（NMOSD）患者中的 N-MOmentum 试验中对扩展残疾状况量表（EDSS）评分恶化和改良 Rankin 量表（mRS）评分的治疗效果。

方法

纳入 230 例水通道蛋白 4 免疫球蛋白 G 阳性 NMOSD 或 -阴性视神经脊髓炎患者，EDSS 评分≤8，随机（3:1）接受伊奈利珠单抗 300mg 或安慰剂治疗，在第 1 天和第 15 天给药。随机对照期（RCP）为 28 周或直至判定为发作，可选择进入伊奈利珠单抗开放标签期。采用 Cox 比例风险模型评估 3 个月 EDSS 确认的残疾进展（CDP）。通过交互检验评估基线亚组对残疾的影响。通过 Wilcoxon-Mann-Whitney 比值比方法分析 RCP 期间的 mRS 评分。

结果

与安慰剂相比，伊奈利珠单抗降低了 3 个月 CDP 的风险（风险比 [HR]：0.375；95%CI：0.148-0.952； = 0.0390）。基线残疾、研究前发作频率和疾病持续时间不影响伊奈利珠单抗的治疗效果（HRs：0.213-0.503；交互检验：所有 > 0.05，表明基线协变量对结局无影响）。随着长期治疗，平均 EDSS 评分有所改善。伊奈利珠单抗治疗的参与者在 RCP 结束时更有可能获得有利的 mRS 结局（OR：1.663；95%CI：1.195-2.385； = 0.0023）。