加奈珠单抗与安慰剂治疗发作性和慢性偏头痛的获益-风险评估：基于需要治疗人数和需要治疗危害人数的指标。

Benefit-Risk Assessment of Galcanezumab Versus Placebo for the Treatment of Episodic and Chronic Migraine Using the Metrics of Number Needed to Treat and Number Needed to Harm.

机构信息

Department of Psychiatry & Behavioral Sciences, New York Medical College, Valhalla, NY, USA.

Neurology Department, Clínica Universidad de Navarra, Madrid, Spain.

出版信息

Adv Ther. 2021 Aug;38(8):4442-4460. doi: 10.1007/s12325-021-01848-x. Epub 2021 Jul 15.

DOI:10.1007/s12325-021-01848-x

PMID:34264500

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8342379/

Abstract

INTRODUCTION

Subcutaneous galcanezumab was an effective, well-tolerated preventive treatment for adults with episodic (EM) or chronic migraine (CM) in 4 phase 3 randomized controlled trials: EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER. Number needed to treat (NNT) and to harm (NNH) are metrics of effect size used to evaluate benefit-risk profiles. This study evaluated NNT, NNH, and benefit-risk profiles (measured as likelihood to be helped or harmed, LHH) of galcanezumab 120 mg versus placebo in patients with EM or CM.

METHODS

Primary efficacy outcomes were responses defined as ≥ 30%, ≥ 50%, and ≥ 75% reductions from baseline in number of monthly migraine headache days in patients with EM (EVOLVE-1; EVOLVE-2; CONQUER) and CM (REGAIN; CONQUER); corresponding NNTs to achieve respective responses; and corresponding NNHs for discontinuations due to adverse events (DCAEs) among the safety population. Secondary efficacy outcomes were responses for patients with ≥ 2 failed prior preventive treatments due to lack of efficacy and/or for tolerability reasons. All LHHs were based on ≥ 50% response and DCAEs.

RESULTS

During double-blind treatment periods with galcanezumab 120 mg, NNT to achieve ≥ 30% and ≥ 50% responses ranged from 4 to 10 and NNT to achieve ≥ 75% responses ranged from 5 to 23 in individual trials. NNH ranged from 93 to 1000, while LHH ranged from 18.6 to 104.6. NNTs were generally more robust among patients with EM than with CM; however, in patients with failure of ≥ 2 prior preventive treatments, NNTs to achieve ≥ 30% and ≥ 50% responses were similar between patients with CM and EM. NNHs were imputed as 1000 for both migraine types. Resulting LHHs were 178.8 (EM) and 127 (CM).

CONCLUSION

Across 4 trials, galcanezumab 120 mg demonstrated a favorable benefit-risk profile versus placebo, based on low NNTs to achieve response and high NNHs associated with DCAEs. LHH values consistently far exceeded 1.

TRIAL REGISTRATION NUMBERS

EVOLVE-1: ClinicalTrials.gov identifier, NCT02614183; EVOLVE-2: ClinicalTrials.gov identifier, NCT02614196; REGAIN: ClinicalTrials.gov identifier, NCT02614261; CONQUER: ClinicalTrials.gov identifier, NCT03559257.

摘要

简介

在四项 3 期随机对照试验中，皮下型加奈珠单抗对发作性偏头痛（EM）或慢性偏头痛（CM）成年患者是一种有效且耐受良好的预防治疗药物：EVOLE-1、EVOLE-2、REGAIN 和 CONQUER。需要治疗的人数（NNT）和需要伤害的人数（NNH）是用于评估获益风险特征的效应大小的衡量指标。本研究评估了在 EM 或 CM 患者中，加奈珠单抗 120mg 与安慰剂相比的 NNT、NNH 和获益风险状况（以获益或伤害的可能性衡量，LHH）。

方法

主要疗效终点是在 EVOLVE-1、EVOLVE-2 和 CONQUER 中，EM 患者的每月偏头痛头痛天数从基线减少≥30%、≥50%和≥75%的反应定义；在 REGAI 和 CONQUER 中，CM 患者的每月偏头痛头痛天数从基线减少≥30%、≥50%和≥75%的反应定义；达到各自反应的相应 NNT；以及安全性人群中因不良反应（AE）停药的相应 NNH。次要疗效终点是在因疗效不佳和/或不耐受而导致≥2 次预防治疗失败的患者中的反应。所有 LHH 均基于≥50%的反应和 AE。

结果

在加奈珠单抗 120mg 的双盲治疗期间，在个别试验中，达到≥30%和≥50%反应的 NNT 范围为 4-10，达到≥75%反应的 NNT 范围为 5-23。NNH 范围为 93-1000，而 LHH 范围为 18.6-104.6。在 EM 患者中，NNT 通常比 CM 患者更稳健；然而，在≥2 次预防治疗失败的患者中，CM 和 EM 患者达到≥30%和≥50%反应的 NNT 相似。NNH 均被推断为 1000，适用于两种偏头痛类型。由此产生的 LHH 值分别为 178.8（EM）和 127（CM）。

结论

在四项试验中，加奈珠单抗 120mg 与安慰剂相比，具有良好的获益风险特征，这基于实现反应的低 NNT 和与 AE 相关的高 NNH。LHH 值始终远远超过 1。

试验登记号

EVOLE-1：ClinicalTrials.gov 标识符，NCT02614183；EVOLE-2：ClinicalTrials.gov 标识符，NCT02614196；REGAI：ClinicalTrials.gov 标识符，NCT02614261；CONQUER：ClinicalTrials.gov 标识符，NCT03559257。