Risk–Benefit Analysis of Novel Treatments for Patients with Generalized Myasthenia Gravis

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Advances in Therapy Pub Date : 2024-10-29 DOI:10.1007/s12325-024-03014-5

A. Gordon Smith, Gil I. Wolfe, Ali A. Habib, Cynthia Z. Qi, Hongbo Yang, Mandy Du, Xin Chen, Deborah Gelinas, Edward Brauer, Glenn Phillips, Francesco Saccà

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Abstract

Introduction

This study used network meta-analysis (NMA) to inform and compare the number needed to treat (NNT), number needed to harm (NNH), and cost per improved outcome (CPIO) associated with more recently approved treatments for anti-acetylcholine receptor antibody-positive (anti-AChR Ab+) generalized myasthenia gravis (gMG).

Methods

Clinical trials of neonatal Fc receptor (FcRn) inhibitors, efgartigimod intravenous (IV) and rozanolixizumab, and complement inhibitors, ravulizumab and zilucoplan, versus placebo (with background conventional treatment) were included in the primary NMA to compare efficacy and safety outcomes. The outputs from the NMAs were used to estimate NNT and NNH of each treatment versus placebo. CPIO (2024 USD) was estimated for a ≥ 3- or ≥ 5-point reduction from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores. Sensitivity analyses were performed adding efgartigimod PH20 subcutaneous (SC) and eculizumab to the NMA.

Results

Efgartigimod IV had the lowest NNT versus placebo for achieving a ≥ 3- and ≥ 5-point reduction in QMG, as well as a ≥ 5-point reduction in MG-ADL, whereas rozanolixizumab had the lowest NNT for a ≥ 3-point reduction in MG-ADL. The NNH versus placebo was similar across comparator treatments. Efgartigimod IV had the lowest CPIO among all treatments for all assessed efficacy outcomes. Sensitivity analyses yielded results consistent with primary analysis and indicated that efgartigimod PH20 SC had comparable NNT and CPIO values to efgartigimod IV, whereas eculizumab had comparable NNT and higher CPIO values compared to other complement inhibitors.

Conclusions

FcRn inhibitors and complement inhibitors assessed in this study all demonstrated clinical benefit in terms of NNT as well as an acceptable safety profile in terms of NNH. Within the limitations of this meta-analysis, efgartigimod was associated with a favorable benefit–risk profile as well as a better economic value compared to ravulizumab, rozanolixizumab, and zilucoplan as treatments for anti-AChR Ab+ gMG.

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全身性肌无力患者新疗法的风险效益分析

简介：本研究采用网络荟萃分析（NMA），对最近批准的抗乙酰胆碱受体抗体阳性（anti-AChR Ab+）全身性肌无力（gMG）治疗方法的相关治疗所需人数（NNT）、伤害所需人数（NNH）和每次改善结果的成本（CPIO）进行了分析和比较：新生儿 Fc 受体 (FcRn) 抑制剂依加替莫德静脉注射 (IV) 和罗扎诺利珠单抗，以及补体抑制剂雷珠单抗和齐鲁珠单抗与安慰剂（背景常规治疗）的临床试验被纳入主要 NMA，以比较疗效和安全性结果。NMA 的结果用于估算每种疗法与安慰剂相比的 NNT 和 NNH。定量肌无力（QMG）和肌无力-日常生活活动（MG-ADL）评分比基线降低≥3 分或≥5 分时，估算 CPIO（2024 美元）。在NMA的基础上增加了依加替莫德PH20皮下注射（SC）和依库珠单抗，进行了敏感性分析：与安慰剂相比，依加替莫德 IV 在实现 QMG 降低≥ 3 分和≥ 5 分以及 MG-ADL 降低≥ 5 分方面的 NNT 最低，而罗扎尼珠单抗在实现 MG-ADL 降低≥ 3 分方面的 NNT 最低。与安慰剂相比，各种比较治疗的NNH相似。在所有疗效评估结果中，依加替莫德 IV 的 CPIO 最低。敏感性分析得出的结果与主要分析一致，表明依夫加替莫德PH20 SC的NNT和CPIO值与依夫加替莫德IV相当，而与其他补体抑制剂相比，依库珠单抗的NNT相当，CPIO值较高：结论：本研究评估的 FcRn 抑制剂和补体抑制剂都显示出了 NNT 方面的临床获益以及 NNH 方面可接受的安全性。在这项荟萃分析的局限性范围内，与雷珠单抗、罗扎尼珠单抗和齐鲁戈兰相比，依加替莫德在治疗抗ACHR Ab+ gMG方面具有良好的获益-风险特征和更高的经济价值。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) 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 therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in 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.