Centre de Ressources et Compétences Sclérose En Plaques, Neurologie, Université Nice Côte d'Azur, CHU Pasteur 2, 30 voie Romaine, 06002, Nice, France.
Centre Régional de Pharmacovigilance, CHU Cimiez, Nice, France.
CNS Drugs. 2018 Oct;32(10):939-949. doi: 10.1007/s40263-018-0564-y.
In the 1990s, the first disease-modifying therapies (DMTs) for multiple sclerosis (MS) were injectable immunomodulatory (IM) drugs, including four different interferon-β preparations and glatiramer acetate. Since 2000, more than 15 immunosuppressant (IS) drugs have been used, with a more or less specific action on inflammation. These include monoclonal antibodies targeting CTL4, the integrin receptor, the interleukin (IL)-2 receptor, CD19, CD20, CD52, and the sphingosine 1 phosphate family. The association between MS and cancer has long been investigated but has led to conflicting results. No studies have reported an increased risk of cancer after long-term exposure to IM. Several reports suggest an increase in cancer risk among MS patients treated with IS such as mitoxantrone, azathioprine and cyclophosphamide. Because of their action on the immune system, and due to a lack of available long-term data, a special warning of the potential risk of cancer accompanies the use of recent IS such as cladribine, fingolimod, natalizumab or alemtuzumab. In most studies, factors such as diet, smoking, solar radiation, and hormone therapy, all of which influence cancer risk, have not been considered. For fingolimod, natalizumab, alemtuzumab, dimethyl fumarate, teriflunomide, daclizumab and ocrelizumab, risk management plans outlined by regulatory agencies are mandatory. They allow prospective detection of some red flags, in particular those for the increased risk of cancer. We review the current evidence behind the increased risk of malignancy in MS patients receiving DMTs, and provide an overview of the DMTs that are currently in use and those in clinical trials. The known risks and benefits of these therapies will be considered.
20 世纪 90 年代，首批多发性硬化症（MS）的疾病修正疗法（DMT）为可注射免疫调节（IM）药物，包括四种不同的干扰素-β制剂和醋酸格拉替雷。自 2000 年以来，已有 15 多种免疫抑制剂（IS）药物被使用，它们对炎症具有或多或少的特异性作用。这些药物包括靶向 CTL4、整合素受体、白细胞介素（IL）-2 受体、CD19、CD20、CD52 和鞘氨醇 1 磷酸家族的单克隆抗体。MS 与癌症之间的关联早已被研究，但结果却相互矛盾。长期使用 IM 并未报告癌症风险增加。一些报告表明，接受 IS 治疗（如米托蒽醌、硫唑嘌呤和环磷酰胺）的 MS 患者癌症风险增加。由于它们对免疫系统的作用，以及缺乏长期可用数据， cladribine、fingolimod、natalizumab 或 alemtuzumab 等最近的 IS 药物的使用伴随着潜在癌症风险的特殊警告。在大多数研究中，没有考虑到影响癌症风险的因素，如饮食、吸烟、太阳辐射和激素治疗。对于 fingolimod、natalizumab、alemtuzumab、dimethyl fumarate、teriflunomide、daclizumab 和 ocrelizumab，监管机构概述的风险管理计划是强制性的。它们允许前瞻性检测一些危险信号，特别是那些癌症风险增加的信号。我们回顾了接受 DMT 的 MS 患者恶性肿瘤风险增加的现有证据，并概述了目前正在使用和临床试验中的 DMT。将考虑这些疗法的已知风险和益处。
