Safety Monitoring of Omaveloxolone in Friedreich Ataxia: Results from One Year of Clinical Treatment.

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Neurology and Therapy Pub Date : 2025-06-01 Epub Date: 2025-04-30 DOI:10.1007/s40120-025-00749-3

Katherine Gunther, Victoria Profeta, Medina Keita, Courtney Park, McKenzie Wells, Sonal Sharma, Kimberly Schadt, David R Lynch

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引用次数: 0

Abstract

Introduction: Omaveloxolone, the only approved medication for Friedreich ataxia (FRDA), is an NRF2 activator available since July 2023. We examined safety monitoring of omaveloxolone administration over the first 12 months of administration.

Methods: We recorded baseline and follow-up serum transaminase, albumin, total bilirubin, cholesterol, and brain natriuretic peptide (BNP) values as well as adverse events over 1 year in patients initiating commercial omaveloxolone therapy.

Results: Access to omaveloxolone was obtained in 236 of individuals for whom it was prescribed. Side effects were noted in 23.8% of patient with the most common being gastrointestinal upset, headache, and fatigue baseline. Twenty-one patients (8.9%) permanently discontinued the drug during the first year. Over the first year, 56.6% of patients had at least one transaminase value above the upper limit of normal at some point. Elevations largely occurred over the first 3 months of therapy, and after 6 months of dosing, only 8.6% of patients had elevations in transaminases. Elevations were generally < 3 × the upper limit of normal and decreased with temporary pausing of the drug or dose reduction. Few changes were noted in albumin or bilirubin, and such changes did not parallel changes in transaminases, suggesting they are independent events. BNP values were generally unchanged throughout the year, and no systematic changes in blood counts were noted. Cholesterol and low-density lipoprotein (LDL) elevations were mild.

Conclusions: Most patients with FRDA eventually had access to omaveloxolone, and it was generally well tolerated. Side effects were modest, and, overall, most patients remained on the drug. Abnormalities in serum liver function tests were limited to transaminases, resolved with dose pausing or reduction, and diminished markedly over time. Thus, the safety features of omaveloxolone after administration largely resemble the favorable features noted during clinical trials.

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奥米洛龙治疗弗里德赖希共济失调的安全性监测：一年临床治疗的结果。

简介：Omaveloxolone是唯一被批准用于治疗弗里德赖希共济失调（FRDA）的药物，是一种NRF2激活剂，于2023年7月上市。我们在给药的前12个月检查了奥马韦洛龙给药的安全性监测。方法：我们记录了基线和随访的血清转氨酶、白蛋白、总胆红素、胆固醇和脑利钠肽（BNP）值，以及在1年内开始使用商业奥马维洛酮治疗的患者的不良事件。结果：在236名处方患者中获得了奥马维洛酮。23.8%的患者出现副作用，最常见的是胃肠道不适、头痛和疲劳基线。21名患者（8.9%）在第一年永久停药。在第一年，56.6%的患者至少有一个转氨酶值高于正常上限。转氨酶升高主要发生在治疗的前3个月，在给药6个月后，只有8.6%的患者转氨酶升高。升高一般<正常值上限的3倍，并随暂时停药或减量而降低。白蛋白或胆红素的变化很少，而且这种变化与转氨酶的变化不平行，表明它们是独立的事件。全年BNP值基本不变，血球计数无系统性变化。胆固醇和低密度脂蛋白（LDL）升高轻微。结论：大多数FRDA患者最终获得了奥马维洛酮，并且通常耐受性良好。副作用不大，总体而言，大多数患者仍在服用该药。血清肝功能检查的异常仅限于转氨酶，随着剂量暂停或减少而消失，并随着时间的推移而明显减少。因此，奥马洛龙给药后的安全性特征在很大程度上类似于临床试验中注意到的有利特征。

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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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