Managing Aminotransferase Elevations in Patients with Friedreich Ataxia Treated with Omaveloxolone: A Review and Expert Opinion on Use Considerations.

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Neurology and Therapy Pub Date : 2025-06-02 DOI:10.1007/s40120-025-00752-8

Susan Perlman, Mathieu Anheim, Sylvia Boesch, James H Lewis, David R Lynch

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引用次数: 0

Abstract

Omaveloxolone is approved for the treatment of Friedreich ataxia (FA) in patients aged ≥ 16 years and is under clinical development for pediatric patients. In the MOXIe study, alanine and aspartate aminotransferase (ALT and AST) elevations were among the most common treatment-emergent adverse events (TEAEs) in the omaveloxolone arm and were mild to moderate, generally asymptomatic, transient, and reversible; no patients who received omaveloxolone had laboratory abnormalities that met the Hy's law criteria. Omaveloxolone labels (US and EU) provide guidance for monitoring and managing these elevations. Here, practical use considerations, from experience-based opinions of four FA experts and a hepatologist via semi-structured interviews, are presented. Prior to omaveloxolone initiation, assessment of baseline ALT, AST, and total bilirubin is recommended per label. During treatment, ALT, AST, and total bilirubin should be monitored monthly for the first 3 months and periodically thereafter per label. Reduced frequency of patient monitoring after 3 months is suggested if aminotransferase levels remain normal. Per label, omaveloxolone should be temporarily discontinued if aminotransferases increase to > 5 × the upper limit of normal (ULN) or > 3 × ULN with other evidence of liver dysfunction. Stemming from real-world practical considerations wherein patients are followed up less frequently than in the trial setting, treatment interruption when aminotransferases increase to ≥ 3 × ULN without other signs of hepatic impairment may be considered. When aminotransferase elevations stabilize or resolve, omaveloxolone may be reinitiated with an appropriate increased frequency of monitoring of liver function per label. We propose patients who pause treatment may have testing repeated after 2 weeks, while those with resolving aminotransferase elevations may reinitiate omaveloxolone with stepwise dose titrations and testing every 2 weeks for ≈ 3 months. Use considerations herein may inform decisions on monitoring and managing ALT and AST elevations, which potentially help to encourage the treatment adherence needed to achieve the slowing of FA progression seen in MOXIe.Graphical abstract available for this article.

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奥米洛龙治疗弗里德赖希共济失调患者转氨酶升高的管理：综述和使用考虑的专家意见。

Omaveloxolone被批准用于治疗年龄≥16岁的弗里德赖希共济失调（FA）患者，目前正在临床开发用于儿科患者。在MOXIe研究中，丙氨酸和天冬氨酸转氨酶（ALT和AST）升高是奥马洛龙治疗组中最常见的治疗不良事件（teae）之一，为轻度至中度，通常无症状，短暂且可逆；接受奥马维洛酮治疗的患者没有实验室异常符合希氏法标准。奥马维洛酮标签（美国和欧盟）提供了监测和管理这些升高的指导。在这里，从四位FA专家和一位肝病学家通过半结构化访谈的经验为基础的意见，提出了实际使用的考虑。在开始使用奥马洛酮之前，推荐每个标签评估基线ALT、AST和总胆红素。治疗期间，前3个月应每月监测ALT、AST和总胆红素，此后每个标签定期监测。如果转氨酶水平保持正常，建议在3个月后减少患者监测频率。根据说明书，如果转氨酶升高至正常值上限（ULN）的5倍或3倍，并伴有其他肝功能障碍，则应暂时停用奥马洛酮。由于现实世界的实际考虑，患者的随访频率低于试验环境，当转氨酶增加到≥3 × ULN而没有其他肝功能损害迹象时，可以考虑中断治疗。当转氨酶升高稳定或消退时，可重新开始使用奥马维洛酮，并适当增加每个标签监测肝功能的频率。我们建议暂停治疗的患者可以在2周后重复检测，而转氨酶升高的患者可以重新开始使用奥马维洛酮，逐步滴定剂量，每2周检测一次，持续约3个月。在此，使用考虑因素可以为监测和管理ALT和AST升高的决策提供信息，这可能有助于鼓励治疗依从性，以实现减缓MOXIe中FA进展的目标。本文提供图形摘要。

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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. 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