Diem Lara, Nedeltchev Krassen, Kahles Timo, Achtnichts Lutz, Findling Oliver
Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
Department of Neurology, Cantonal Hospital Aarau, Tellstrasse, Aarau 5000, Switzerland.
Ther Adv Neurol Disord. 2018 Aug 9;11:1756286418791103. doi: 10.1177/1756286418791103. eCollection 2018.
Natalizumab significantly reduces the disease activity in patients with relapsing-remitting multiple sclerosis but due to the risk of progressive multifocal leukoencephalopathy it is often discontinued. Fingolimod is seen as an alternative, but there are no long-term analyses of the efficacy of fingolimod in this setting using the no evidence of disease activity (NEDA)-3 criteria. We provide an assessment of patients who discontinued natalizumab and switched to fingolimod or other treatments by evaluating the proportion of patients who fulfil NEDA-3 criteria after prolonged follow-up periods.
We conducted a retrospective observational study of multiple sclerosis patients, who were treated with continuous natalizumab or who had switched to fingolimod or other treatments after natalizumab discontinuation. We assessed NEDA-3 status, annual relapse rate and determined the odds ratio between disease course after treatment switch and other patient and treatment characteristics.
A total of 61 patients on continuous natalizumab treatment and 53 patients who switched from natalizumab to fingolimod or other treatments were accompanied for up to 5 years. While the proportion of natalizumab patients fulfilling NEDA-3 criteria remained stable at 90% during the entire follow-up period, the proportion of patients switching to fingolimod or other therapies dropped to 76.7% in the first year after discontinuation, and to 50% in the years thereafter. While the median Expanded Disability Status Scale remained stable and the percentage of relapsing patients did not change significantly, recurring magnetic resonance imaging activity was found in up to 42% of the patients after switching from natalizumab to other treatments. New disease activity was significantly correlated with extended treatment gap between natalizumab discontinuation and the start of a new therapy.
Patients remain clinically stable after discontinuing natalizumab and switching to other therapies. However, when considering NEDA-3 criteria, a considerable proportion of patients show disease reactivation. Careful monitoring and early evaluation of alternatives is necessary after switching from natalizumab to other treatments.
那他珠单抗可显著降低复发缓解型多发性硬化症患者的疾病活动度，但由于存在进展性多灶性白质脑病风险，该药物常被停用。芬戈莫德被视为一种替代药物，但目前尚无使用无疾病活动证据（NEDA）-3标准对芬戈莫德在此情况下疗效的长期分析。我们通过评估在延长随访期后达到NEDA-3标准的患者比例，对停用那他珠单抗并改用芬戈莫德或其他治疗的患者进行了评估。
我们对多发性硬化症患者进行了一项回顾性观察研究，这些患者接受了持续的那他珠单抗治疗，或在停用那他珠单抗后改用了芬戈莫德或其他治疗。我们评估了NEDA-3状态、年复发率，并确定了治疗转换后疾病进程与其他患者及治疗特征之间的比值比。
共有61例接受持续那他珠单抗治疗的患者以及53例从那他珠单抗改用芬戈莫德或其他治疗的患者接受了长达5年的随访。在整个随访期间，达到NEDA-3标准的那他珠单抗患者比例保持在90%稳定水平，而改用芬戈莫德或其他治疗的患者比例在停药后的第一年降至76.7%，此后几年降至50%。虽然扩展残疾状态量表中位数保持稳定，复发患者百分比没有显著变化，但在从那他珠单抗改用其他治疗后，高达42%的患者出现了复发性磁共振成像活动。新的疾病活动与那他珠单抗停药至新疗法开始之间的延长治疗间隔显著相关。
患者在停用那他珠单抗并改用其他疗法后临床保持稳定。然而，考虑NEDA-3标准时，相当一部分患者出现疾病再激活。从那他珠单抗改用其他治疗后，需要进行仔细监测并尽早评估替代方案。
