Network Meta-analysis of Ravulizumab and Alternative Interventions for the Treatment of Neuromyelitis Optica Spectrum Disorder.

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Neurology and Therapy Pub Date : 2024-06-01 Epub Date: 2024-05-09 DOI:10.1007/s40120-024-00597-7

Stacey L Clardy, Sean J Pittock, Orhan Aktas, Jin Nakahara, Noriko Isobe, Diego Centonze, Sami Fam, Adrian Kielhorn, Jeffrey C Yu, Jeroen Jansen, Ina Zhang

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引用次数: 0

Abstract

Introduction: Anti-aquaporin-4 antibody-positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) is a complement-mediated autoimmune disease in which unpredictable and relapsing attacks on the central nervous system cause irreversible and accumulating damage. Comparative efficacy of new NMOSD therapies, such as ravulizumab, with established therapies is critical in making informed treatment decisions.

Methods: Efficacy of ravulizumab relative to established AQP4-Ab+ NMOSD treatments, such as eculizumab, inebilizumab, and satralizumab, was evaluated in a Bayesian network meta-analysis (NMA). Data were extracted from trials identified by a systematic literature review. The final evidence base consisted of 17 publications representing five unique and global studies (PREVENT, N-MOmentum, SAkuraSky, SAkuraStar, and CHAMPION-NMOSD). The primary endpoint was time-to-first relapse; other outcomes included annualized relapse rates (ARRs).

Results: For patients receiving monotherapy (monoclonal antibody only), ravulizumab was associated with a lower risk of relapse than inebilizumab (hazard ratio [HR] 0.09, 95% credible interval [CrI] 0.02, 0.57) or satralizumab (HR 0.08, 95% CrI 0.01, 0.55) and was comparable to eculizumab (HR 0.86, 95% Crl 0.16, 4.52). Ravulizumab + immunosuppressive therapy (IST) was associated with a lower risk of relapse than satralizumab + IST (HR 0.15, 95% CrI 0.03, 0.78); the comparison with eculizumab + IST suggested no difference. No patients treated with inebilizumab received background IST and were thus excluded from analysis. The ARR with ravulizumab monotherapy was 98% lower compared with inebilizumab (rate ratio [RR] 0.02, 95% Crl 0.00, 0.38) and satralizumab (RR 0.02, 95% Crl 0.00, 0.42) monotherapies. The ARR with ravulizumab ± IST showed the strongest treatment-effect estimates compared with other interventions.

Conclusion: In the absence of head-to-head randomized controlled trials, NMA results suggest ravulizumab, a C5 inhibitor, is likely to be more effective in preventing NMOSD relapse in patients with AQP4-Ab+ NMOSD when compared with other treatments having different methods of action.

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治疗神经脊髓炎视网膜频谱紊乱症的雷珠单抗和替代干预措施的网络 Meta 分析。

导言：抗quaporin-4抗体阳性（AQP4-Ab+）神经脊髓炎视谱系障碍（NMOSD）是一种补体介导的自身免疫性疾病，中枢神经系统受到不可预测的复发性攻击，造成不可逆转的累积性损伤。新的NMOSD疗法（如雷夫利珠单抗）与既有疗法的疗效比较对于做出明智的治疗决策至关重要：在贝叶斯网络荟萃分析（NMA）中评估了雷珠单抗相对于AQP4-Ab+ NMOSD既有疗法（如eculizumab、inebilizumab和satralizumab）的疗效。数据提取自系统性文献综述所确定的试验。最终的证据基础包括 17 篇出版物，代表了五项独特的全球性研究（PREVENT、N-MOmentum、SAkuraSky、SAkuraStar 和 CHAMPION-NMOSD）。主要终点是首次复发时间；其他结果包括年复发率（ARR）：结果：对于接受单药治疗（仅单克隆抗体）的患者，雷珠单抗的复发风险低于伊匹单抗（危险比[HR]0.09，95%可信区间[CrI]0.02，0.57）或沙妥珠单抗（HR 0.08，95%可信区间0.01，0.55），与依库珠单抗相当（HR 0.86，95%可信区间0.16，4.52）。雷珠单抗+免疫抑制疗法（IST）的复发风险低于萨曲单抗+IST（HR 0.15，95% CrI 0.03，0.78）；与依库珠单抗+IST的比较结果显示两者没有差异。没有接受伊匹单抗治疗的患者接受了背景 IST，因此未纳入分析。与依维珠单抗（比率比[RR] 0.02，95% Crl 0.00，0.38）和萨他利珠单抗（RR 0.02，95% Crl 0.00，0.42）单一疗法相比，拉武利珠单抗单一疗法的ARR降低了98%。与其他干预措施相比，雷珠单抗±IST的ARR显示出最强的治疗效果估计值：在缺乏头对头随机对照试验的情况下，NMA结果表明，与其他具有不同作用方式的治疗方法相比，C5抑制剂雷珠单抗可能更有效地预防AQP4-Ab+ NMOSD患者的NMOSD复发。

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来源期刊

Neurology and Therapy CLINICAL NEUROLOGY-

CiteScore

5.40

自引率

8.10%

发文量

103

审稿时长

6 weeks

期刊介绍： Aims and Scope Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice. Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Neurology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted, it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model, this allows for the rapid and efficient communication of the latest research and reviews to support scientific discovery and clinical practice. Open Access All articles published by Neurology and Therapy are open access. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts. 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