Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nürnberg, Germany.
Department of Neurology, Klinikum Augsburg, Augsburg, Germany.
J Neurol. 2018 Jul;265(7):1521-1527. doi: 10.1007/s00415-018-8871-2. Epub 2018 Apr 25.
Relapsing-remitting multiple sclerosis (RRMS) requires efficient immunomodulatory treatment to reach "no evidence of disease activity" status at best. Alemtuzumab and fingolimod have proved to be efficient options in RRMS with active disease course. Yet, side effects and break-through disease may limit long-time treatment and necessitate switch of medication. Data on efficacy and safety of alemtuzumab following fingolimod treatment are limited, but useful for clinical practice.
Clinical and MRI data of 50 RRMS patients with a history of therapy switch from fingolimod to alemtuzumab were retrospectively analyzed. Data were acquired from nine large German MS Centers from 2013 to 2016 and analyzed using descriptive statistics.
On average, patients with disease duration of 12.9 years and median EDSS of 3.0 at baseline switched to alemtuzumab after 68 weeks of fingolimod treatment. Thereafter, patients on alemtuzumab were followed for a mean of 64 weeks. The annualized relapse rate decreased from 2.2 in the year prior to 0.34 in the following year after switching to alemtuzumab and EDSS stabilized. In a subgroup of patients (n = 23), MRI data point to a reduction in enhancing (4.47 vs. 0.26) and new/enlarging T2 lesions (5.8 vs. 0.27) after treatment adjustment. Side effects were generally as expected from published data for alemtuzumab (autoimmunity 2/50, severe infections 1/50). One patient suffered combined lethal necrotizing leukoencephalopathy and hemolytic anemia.
Therapy switch was highly effective in reducing clinical and MRI surrogates of disease activity and was mainly well tolerated within one year of follow-up. Hence, alemtuzumab constitutes a promising therapy in RRMS with refractory disease activity despite fingolimod treatment. Further studies are warranted to confirm these beneficial findings and to reveal safety concerns in the longer-term follow-up.
复发缓解型多发性硬化症（RRMS）需要有效的免疫调节治疗，以达到最佳的“无疾病活动证据”状态。阿仑单抗和芬戈莫德已被证明在疾病活动期的 RRMS 中是有效的选择。然而，副作用和突破性疾病可能会限制长期治疗，并需要药物转换。关于阿仑单抗在芬戈莫德治疗后的疗效和安全性的数据有限，但对临床实践有用。
回顾性分析了 50 例 RRMS 患者的临床和 MRI 数据，这些患者在接受芬戈莫德治疗后有药物转换史。这些数据来自 2013 年至 2016 年德国 9 个大型 MS 中心，使用描述性统计进行分析。
平均而言，基线时疾病持续时间为 12.9 年，EDSS 中位数为 3.0 的患者在接受芬戈莫德治疗 68 周后转为阿仑单抗治疗。此后，患者接受阿仑单抗治疗的平均时间为 64 周。年复发率从转换前的 2.2 降至转换后的 0.34，EDSS 稳定。在一个亚组患者（n=23）中，MRI 数据显示治疗调整后增强病变（4.47 比 0.26）和新/扩大的 T2 病变（5.8 比 0.27）减少。副作用通常与阿仑单抗的已发表数据一致（自身免疫 2/50，严重感染 1/50）。有 1 例患者发生了致命性坏死性脑白质病和溶血性贫血的合并症。
尽管接受了芬戈莫德治疗，但治疗转换在降低临床和 MRI 疾病活动替代指标方面非常有效，并且在随访的第一年主要是耐受良好的。因此，阿仑单抗在 RRMS 中是一种有前途的治疗方法，尤其是在疾病活动期对芬戈莫德治疗无效的情况下。需要进一步的研究来证实这些有益的发现，并揭示长期随访中的安全性问题。
