在转换为先前的治疗或继续使用 DRF 后，富马酸二甲酯的疗效和安全性结果：来自 3 期 EVOLVE-MS-1 研究的结果。
Efficacy and Safety Outcomes with Diroximel Fumarate After Switching from Prior Therapies or Continuing on DRF: Results from the Phase 3 EVOLVE-MS-1 Study.
机构信息
Hope Neurology MS Center, Knoxville, TN, USA.
Department of Neurology, University of Leipzig, Leipzig, Germany.
出版信息
Adv Ther. 2022 Apr;39(4):1810-1831. doi: 10.1007/s12325-022-02068-7. Epub 2022 Feb 24.
INTRODUCTION
Diroximel fumarate (DRF) is an oral fumarate for relapsing multiple sclerosis (MS) with the same active metabolite as dimethyl fumarate (DMF). DRF has a safety/efficacy profile similar to DMF but with improved gastrointestinal (GI) tolerability and low (< 1%) treatment discontinuation due to GI adverse events (AEs). Efficacy and safety outcomes in patients who switched to DRF from other disease-modifying therapies (DMTs) have not been evaluated.
METHODS
EVOLVE-MS-1 is an ongoing, 2-year, open-label, phase 3 study of DRF in adults with relapsing-remitting MS. Patients either entered as newly enrolled to DRF trials, or from the 5-week, randomized, head-to-head, phase 3 EVOLVE-MS-2 study of DRF and DMF. This analysis evaluated safety and GI tolerability in patients continuing on DRF (DRF-rollover) or switching from DMF (DMF-rollover) following EVOLVE-MS-2. Safety and efficacy were evaluated in a subset of newly enrolled patients who had received prior glatiramer acetate (GA; GA/DRF) or interferons (IFN; IFN/DRF) as their most recent DMT, prior to switching to DRF in EVOLVE-MS-1.
RESULTS
As of September 1, 2020, 1057 patients were enrolled in EVOLVE-MS-1, including 166, 182, 239, and 225 patients in the GA/DRF, IFN/DRF, DRF-rollover, and DMF-rollover groups, respectively. Treatment discontinuation due to GI AEs was < 1% in all groups. GA/DRF and IFN/DRF patients experienced improvements from baseline in clinical and radiological efficacy outcomes, including significantly reduced annualized relapse rates. Rollover patients had low rates of new or recurrent GI AEs (DRF-rollover, 26.8%/4.2%; DMF-rollover, 27.1%/4.9%).
CONCLUSION
After 2 years of DRF exposure, patients with prior GA, IFN, or fumarate treatment had safety outcomes consistent with previous fumarate studies. Efficacy in patients with prior GA or IFN treatment was consistent with previous fumarate studies. The data suggest that transition to DRF from GA, IFN, or DMF is a reasonable treatment strategy, with low rates of discontinuation due to GI AEs.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT02634307). INFOGRAPHIC.
简介
富马酸二甲酯（DMF）是一种治疗多发性硬化症（MS）的口服药物，具有相同的活性代谢物。DRF 具有与 DMF 相似的安全性/疗效特征，但胃肠道（GI）耐受性更好，因 GI 不良反应（AE）而停药的比例较低（<1%）。尚未评估从其他疾病修正治疗（DMT）转换为富马酸二甲酯（DRF）的患者的疗效和安全性结果。
方法
EVOLVE-MS-1 是一项正在进行的、为期 2 年的、开放标签、III 期 DRF 治疗复发性 MS 的研究。患者要么是新入组 DRF 试验的患者，要么是来自 5 周、随机、头对头、III 期 EVOLVE-MS-2 研究的 DRF 和 DMF 试验的患者。这项分析评估了在 EVOLVE-MS-2 后继续接受 DRF（DRF-继续治疗）或从 DMF 转换而来的患者（DMF-继续治疗）的安全性和胃肠道耐受性。在 EVOLVE-MS-1 中，在切换至 DRF 之前，有一小部分新入组的患者曾接受过更昔洛韦（GA；GA/DRF）或干扰素（IFN；IFN/DRF）作为最近的 DMT，评估了这些患者的安全性和疗效。
结果
截至 2020 年 9 月 1 日，1057 名患者入组了 EVOLVE-MS-1 研究，其中 GA/DRF、IFN/DRF、DRF-继续治疗和 DMF-继续治疗组分别有 166、182、239 和 225 名患者。所有组中，因胃肠道 AE 而停药的比例均<1%。GA/DRF 和 IFN/DRF 患者的临床和影像学疗效均有改善，包括年复发率显著降低。继续治疗组的新发生或复发胃肠道 AE 发生率较低（DRF-继续治疗组，26.8%/4.2%；DMF-继续治疗组，27.1%/4.9%）。
结论
在接受 DRF 治疗 2 年后，有 GA、IFN 或富马酸治疗史的患者的安全性结果与之前的富马酸研究一致。有 GA 或 IFN 治疗史的患者的疗效与之前的富马酸研究一致。数据表明，从 GA、IFN 或 DMF 转换为 DRF 是一种合理的治疗策略，因胃肠道 AE 而停药的比例较低。
临床试验注册
ClinicalTrials.gov（NCT02634307）。信息图。
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