Bielekova B, Martin R
Cellular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5B-16, 10 Center Drive MSC 1400, Bethesda, MD 20892, USA.
Curr Treat Options Neurol. 1999 Jul;1(3):201-220. doi: 10.1007/s11940-999-0004-x.
Given our current knowledge, there is a need for the early institution of immunomodulatory therapy, especially for patients with poor prognostic factors (motor and cerebellar symptoms, frequent disease exacerbations, and a high level of activity on magnetic resonance imaging ). Patients who progress despite immunomodulatory therapy should be reevaluated in terms of diagnosis, development of neutralizing antibodies, or compliance. If a patient has a partial response to immunomodulatory therapy but his or her disease, as assessed by clinical and MRI criteria, remains very active, every effort should be made to modify disease progression by searching for an immunosuppressive therapy regimen before irreversible and considerable disability has accumulated. For the majority of patients, multiple sclerosis (MS) is a chronic condition. Therefore, until a curative treatment has been developed, the available repertoire of immunosuppressive or immunomodulatory treatments should be assessed with respect to the possibility of long-term use. This is particularly important for new immunosuppressive drugs, such as cladribine or mitoxantrone, or for invasive procedures, such as total lymphoid irradiation or autologous bone marrow transplantation. For the latter treatments, experience with long-term administration is not available or the potential side effects (eg, cardiotoxicity with mitoxantrone) limit the cumulative dose. These considerations may limit long-term administration and thus the general usefulness of some drugs. Even with proven efficacy, we need to define the next step once treatment has to be discontinued. We should also address whether exacerbating disease by discontinuing an effective therapy is a potential hazard. What other therapeutic options remain once the current treatment is discontinued? Answers are not readily available at the moment, but the question should influence our decisions in the selection of traditional, well-studied or new, potentially promising therapies.
鉴于我们目前的认知,有必要尽早开展免疫调节治疗,尤其是对于具有不良预后因素的患者(运动和小脑症状、疾病频繁发作以及磁共振成像显示的高活动水平)。尽管接受了免疫调节治疗仍出现病情进展的患者,应在诊断、中和抗体的产生或依从性方面进行重新评估。如果患者对免疫调节治疗有部分反应,但根据临床和MRI标准评估其疾病仍非常活跃,则应尽一切努力在不可逆的严重残疾累积之前,通过寻找免疫抑制治疗方案来改变疾病进展。对于大多数患者来说,多发性硬化症(MS)是一种慢性病。因此,在开发出治愈性治疗方法之前,应评估现有的免疫抑制或免疫调节治疗方法长期使用的可能性。这对于新的免疫抑制药物,如克拉屈滨或米托蒽醌,或对于侵入性程序,如全身淋巴照射或自体骨髓移植尤为重要。对于后一种治疗方法,缺乏长期给药的经验,或者潜在的副作用(如米托蒽醌的心脏毒性)限制了累积剂量。这些考虑因素可能会限制某些药物的长期给药,从而限制其总体实用性。即使已证明疗效,我们也需要确定一旦停止治疗后的下一步措施。我们还应探讨停止有效治疗是否会使疾病恶化这一潜在风险。一旦停止当前治疗,还有哪些其他治疗选择?目前尚无现成的答案,但这个问题应影响我们在选择传统的、经过充分研究的或新的、可能有前景的治疗方法时的决策。