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富马酸二甲酯:多发性硬化症患者常见不良事件的疗效及实际管理策略综述

Dimethyl Fumarate: A Review of Efficacy and Practical Management Strategies for Common Adverse Events in Patients with Multiple Sclerosis.

作者信息

Phillips J Theodore, Agrella Stephanie, Fox Robert J

出版信息

Int J MS Care. 2017 Mar-Apr;19(2):74-83. doi: 10.7224/1537-2073.2015-086.

DOI:10.7224/1537-2073.2015-086
PMID:32607065
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7313409/
Abstract

BACKGROUND

Delayed-release dimethyl fumarate (DMF; also known as gastroresistant DMF) is indicated for the treatment of relapsing multiple sclerosis. Flushing and gastrointestinal (GI) adverse events (AEs) are common within the first few months of starting DMF therapy. Although most symptoms are mild or moderate in severity, transient, and infrequently result in treatment discontinuation, they nevertheless present a challenge for patients to adhere to therapy and achieve an optimal treatment response.

METHODS

This review discusses management strategies for the prophylaxis and treatment of common DMF-associated AEs based on clinical trial evidence and real-world experience in clinical practice settings.

RESULTS

Before starting DMF therapy, patients should receive counseling on the importance of treatment adherence and the likely occurrence and severity of flushing and GI AEs (nausea, vomiting, diarrhea, and abdominal pain). Management strategies, such as administering DMF with food, using a slower-dose titration schedule, applying temporary dose reductions, and using symptomatic therapies, provide clinicians with several approaches to address DMF tolerability. In particular, DMF coadministration with certain foods (eg, sausage, peanut butter) may prevent or reduce the severity of GI AEs. Taking aspirin 325 mg/day 30 minutes before administering DMF in the first month of therapy can reduce the incidence and severity of flushing without negatively affecting GI-related events.

CONCLUSIONS

Through continual patient education and support and management of treatment-related flushing and GI AEs, clinicians can help patients adhere to and persist with DMF therapy, thus maximizing treatment benefit.

摘要

背景

缓释富马酸二甲酯(DMF;也称为胃内滞留型DMF)适用于复发型多发性硬化症的治疗。潮红和胃肠道(GI)不良事件(AE)在开始DMF治疗的最初几个月内很常见。尽管大多数症状严重程度为轻度或中度,是短暂性的,很少导致治疗中断,但它们仍然给患者坚持治疗并获得最佳治疗反应带来挑战。

方法

本综述基于临床试验证据和临床实践中的实际经验,讨论了预防和治疗常见DMF相关AE的管理策略。

结果

在开始DMF治疗前,应向患者提供咨询,告知其坚持治疗的重要性以及潮红和胃肠道AE(恶心、呕吐、腹泻和腹痛)可能的发生情况及严重程度。管理策略,如与食物一起服用DMF、采用较慢的剂量滴定方案、暂时减少剂量以及采用对症治疗,为临床医生提供了几种解决DMF耐受性问题的方法。特别是,DMF与某些食物(如香肠、花生酱)同时服用可能预防或减轻胃肠道AE的严重程度。在治疗的第一个月,在服用DMF前30分钟服用325毫克/天的阿司匹林可降低潮红的发生率和严重程度,且不会对胃肠道相关事件产生负面影响。

结论

通过持续的患者教育以及对与治疗相关的潮红和胃肠道AE的管理,临床医生可以帮助患者坚持并持续接受DMF治疗,从而使治疗获益最大化。

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Neurol Clin Pract. 2016 Jun;6(3):220-229. doi: 10.1212/CPJ.0000000000000238.
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Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: Interim analysis of ENDORSE, a randomized extension study.富马酸二甲酯缓释剂治疗多发性硬化症的长期疗效:ENDORSE随机扩展研究的中期分析
Mult Scler. 2017 Feb;23(2):253-265. doi: 10.1177/1352458516649037. Epub 2016 Jul 11.
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Gastrointestinal Tolerability of Delayed-Release Dimethyl Fumarate in a Multicenter, Open-Label Study of Patients with Relapsing Forms of Multiple Sclerosis (MANAGE).富马酸二甲酯缓释制剂在复发型多发性硬化症患者多中心开放标签研究(MANAGE)中的胃肠道耐受性
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4
Delayed-Release Dimethyl Fumarate and Pregnancy: Preclinical Studies and Pregnancy Outcomes from Clinical Trials and Postmarketing Experience.富马酸二甲酯延迟释放剂型与妊娠:临床前研究和临床试验及上市后经验中的妊娠结局。
Neurol Ther. 2015 Dec;4(2):93-104. doi: 10.1007/s40120-015-0033-1. Epub 2015 Oct 12.
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Neurol Ther. 2015 Dec;4(2):137-46. doi: 10.1007/s40120-015-0037-x. Epub 2015 Nov 2.
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