EVOLVE-MS-1三期研究中一组黑人多发性硬化症患者服用富马酸地罗西美酯的安全性、耐受性和疗效。

IF 2.9 3区医学 Q2 CLINICAL NEUROLOGY

Multiple sclerosis and related disorders Pub Date : 2024-09-30 DOI:10.1016/j.msard.2024.105912

Samuel F. Hunter , John W. Lindsey , Benjamin Osborne , Bethany Schreiber , Filipe Branco , Seth Levin , James B. Lewin , Matthew Scaramozza , Zhe Tian , Ariel Antezana

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引用次数: 0

摘要

背景：多发性硬化症（MS）在少数种族和民族中的研究并不深入，因为这些人群在临床试验中的代表性通常不足。美国黑人或非裔美国人占美国总人口的 13%，但在临床试验中仅占 5%。据报道，不同种族和族裔的患者在病程和病情进展方面存在差异，因此有必要了解改变病情疗法（DMTs）在黑人患者中的安全性和有效性，以便为该人群的循证治疗提供依据：EVOLVE-MS-1（NCT0234307）是一项开放标签、单臂、3期研究，评估富马酸双羟吲哚美辛（DRF）对复发缓解型多发性硬化症（RRMS）成人患者96周的长期安全性、耐受性和疗效。患者要么是新开始接受DRF治疗，要么是在完成EVOLVE-MS-2（NCT03093324）治疗后转入DRF治疗。在这项对3期EVOLVE-MS-1研究的事后分析中，我们评估了DRF在黑人和非黑人患者亚组中的安全性和探索性疗效结果：在入组的 1057 例患者中，72 例（6.8%）为黑人。黑人和非黑人患者的平均年龄分别为 42 岁和 43 岁，女性比例分别为 75% 和 72%。两组患者接触 DRF 的时间中位数（范围）均为 1.8（0.0-2.0）年，平均残疾状况扩展量表（EDSS）为 2.7。黑人患者与非黑人患者之前最常用的 DMT 药物分别是干扰素（47% vs 37%）和醋酸格拉替雷（36% vs 24%）。有 33 名黑人患者（46%）和 224 名非黑人患者（23%）中断了 DRF 治疗；黑人患者最常见的中断原因是患者退出（11 人，15.3%）、不良事件（AEs；7 人，9.7%）和失去随访（7 人，9.7%）；非黑人患者的不良事件（8.2%）和患者退出（7.0%）。90%的黑人患者和89%的非黑人患者出现了不良反应；两组患者的不良反应大多为轻度或中度。有 36% 的黑人患者和 32% 的非黑人患者报告了胃肠道 (GI) AE；没有黑人患者因胃肠道 AE 而停药，非黑人患者有 7 例（0.7%）。最常见的不良反应是脸红（黑人患者占 18%，非黑人患者占 28%）。黑人患者中没有出现淋巴细胞减少的不良反应，而非黑人患者中只有 13%。从基线到第 48 周，黑人患者的平均绝对淋巴细胞计数下降了 15%，非黑人患者下降了 29%，然后趋于平稳并保持在正常值下限（LLN；0.91 × 109/L）以上。从 DRF 治疗前 12 个月到治疗后 96 周，黑人患者的调整后年复发率（95% 置信区间）降低了 78.2% (54.6 - 89.5; p < 0.0001)；非黑人患者也降低了 81.7% (78.5 - 84.5%; p < 0.0001)。第48周时，黑人与非黑人患者中证实无残疾进展的平均人数为93.4%，第96周时，黑人与非黑人患者中证实无残疾进展的平均人数分别为86.2%和90.4%：本研究首次对黑人患者使用 DRF 的安全性和有效性进行了分析。接受 DRF 治疗的黑人患者的复发率仍然很低，与非黑人患者一致，而且 EVOLVE-MS-1 在黑人患者亚组中没有发现新的安全信号。这些结果都支持 DRF 成为 RRMS 黑人患者的有效治疗方案。

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Safety, tolerability, and efficacy of diroximel fumarate in a cohort of Black patients with multiple sclerosis from the phase 3 EVOLVE-MS-1 study

Background

Multiple sclerosis (MS) has not been well studied in racial and ethnic minorities, as these populations are typically underrepresented in clinical trials. Black or African Americans comprise ∼13 % of the US population, yet are represented by as little as 5 % in clinical trials. Differences in disease course and progression have been reported between races and ethnicities, so there is a need to understand the safety and efficacy of disease-modifying therapies (DMTs) in Black patients, to inform evidence-based approaches to treatment in this population.

Methods

EVOLVE-MS-1 (NCT0234307) was an open-label, single-arm, phase 3 study assessing the long-term safety, tolerability, and efficacy of diroximel fumarate (DRF) over 96 weeks in adults with relapsing-remitting multiple sclerosis (RRMS). Patients were either newly initiated to DRF or rolled over from completing EVOLVE-MS-2 (NCT03093324). In this post-hoc analysis of the phase 3 EVOLVE-MS-1 study, we evaluate the safety and exploratory efficacy outcomes for DRF in Black and non-Black patient subgroups.

Results

Of 1057 patients enrolled, 72 (6.8 %) were Black. In Black vs non-Black patients, mean age was 42 vs 43 years and 75 % vs 72 % were female, respectively. In both groups, median (range) duration of DRF exposure was 1.8 (0.0–2.0) years and mean Expanded Disability Status Scale (EDSS) was 2.7. The most common prior DMTs for both Black vs non-Black patients were interferons (47 % vs 37 %) and glatiramer acetate (36 % vs 24 %). DRF treatment was discontinued in 33 (46 %) Black and 224 (23 %) non-Black patients; most common reasons for discontinuation were withdrawal by patient (n = 11, 15.3 %), adverse events (AEs; n = 7, 9.7 %), and lost to follow-up (n = 7, 9.7 %) in Black patients; AEs (8.2 %) and withdrawal by patient (7.0 %) in non-Black patients. AEs were reported in 90 % Black and 89 % non-Black patients; most AEs were mild or moderate in both groups. Gastrointestinal (GI) AEs were reported in 36 % Black and 32 % non-Black patients; no Black patients discontinued due to GI AEs, vs 7 (0.7 %) non-Black patients. The most commonly reported AE was flushing (18 % Black and 28 % non-Black patients). No AEs of lymphopenia were reported in Black patients compared with 13 % of non-Black patients. Mean absolute lymphocyte count declined from baseline to week 48 by 15 % in Black patients and 29 % in non-Black patients, then plateaued and remained above the lower limit of normal (LLN; 0.91 × 10⁹/L). Adjusted annualized relapse rate (95 % confidence interval) was reduced by 78.2 % (54.6 − 89.5; p < 0.0001) in Black patients, from 12 months before to 96 weeks after DRF treatment; similar to 81.7 % (78.5 − 84.5 %; p < 0.0001) reduction in non-Black patients. Mean number of patients free from confirmed disability progression was 93.4 % by week 48, then 86.2 % vs 90.4 % by week 96 in Black vs non-Black patients, respectively.

Conclusion

This study presents the first analysis of safety and efficacy of DRF in Black patients. Relapse rates remained low in Black patients on DRF, consistent with non-Black patients, and there were no new safety signals identified in the Black patient subgroup in EVOLVE-MS-1. Together, these outcomes support DRF as an effective treatment option in Black patients with RRMS.

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来源期刊

Multiple sclerosis and related disorders CLINICAL NEUROLOGY-

CiteScore

5.80

自引率

20.00%

发文量

814

审稿时长

66 days

期刊介绍： Multiple Sclerosis is an area of ever expanding research and escalating publications. Multiple Sclerosis and Related Disorders is a wide ranging international journal supported by key researchers from all neuroscience domains that focus on MS and associated disease of the central nervous system. The primary aim of this new journal is the rapid publication of high quality original research in the field. Important secondary aims will be timely updates and editorials on important scientific and clinical care advances, controversies in the field, and invited opinion articles from current thought leaders on topical issues. One section of the journal will focus on teaching, written to enhance the practice of community and academic neurologists involved in the care of MS patients. Summaries of key articles written for a lay audience will be provided as an on-line resource. A team of four chief editors is supported by leading section editors who will commission and appraise original and review articles concerning: clinical neurology, neuroimaging, neuropathology, neuroepidemiology, therapeutics, genetics / transcriptomics, experimental models, neuroimmunology, biomarkers, neuropsychology, neurorehabilitation, measurement scales, teaching, neuroethics and lay communication.