Clinic for Neurology 2, Med Campus III, Kepler University Hospital GmbH, Krankenhausstr. 9, 4021, Linz, Austria.
Medical Faculty, Johannes Kepler University Linz, Linz, Austria.
J Neurol. 2021 Nov;268(11):4303-4310. doi: 10.1007/s00415-021-10559-w. Epub 2021 Apr 22.
To evaluate long-term effectiveness of natalizumab (NTZ) and to determine demographic, clinical, and radiological predictors regarding long-term disease activity (≥ 7 years) in a nationwide observational cohort, using data collected prospectively in a real-life setting.
We analysed data from 230 patients from the Austrian Multiple Sclerosis Treatment Registry (AMSTR), who had started treatment with NTZ at any time since 2006 and stayed on NTZ for at least 7 years without treatment gap of more than three months.
Estimated mean annualised relapse rates (ARR) over a mean treatment period of 9.3 years were 0.07 for NTZ. Sustained EDSS progression for 12 weeks was observed in 36 (19%) patients and for 24 weeks in 31 (16.3%) cases. Sustained EDSS regression for 12 and 24 weeks was seen in 45 (23.7%) and 42 (22.1%) cases. The baseline parameters ≥ 1 Gadolinium-enhancing MRI lesion(s) [incidence rate ratio (IRR) of 0.409 (95% CI 0.283-0.593), p = 0.001], ARR ≤ 1 in the prior 12 month before treatment initiation with NTZ [IRR of 0.353 (95% CI 0.200-0.623), p = 0.001] and EDSS ≤ 1 [incidence rate ratio (IRR) of 0.081 (95% CI 0.011-0.581), p = 0.012] were significantly associated with a reduced relapse risk, whereas a disease duration ≤ 5 years increased significantly the ARR [IRR of 1.851 (95% CI 1.249-2.743), p = 0.002]. The only predictive baseline parameter for experiencing EDSS progression (sustained for 12 and 24 weeks) was age > 35 years [HR of 2.482 (95% CI 1.110-5.549), p = 0.027, and HR of 2.492 (95% CI 1.039-5.978), p = 0.041, respectively].
These real-life data show a stable disease course regarding relapse activity and disease progression under NTZ treatment for more than 7 years. The main predictors for disease activity were higher relapse rate before treatment initiation, higher disability, shorter disease duration and absence of Gadolinium-enhancing MRI lesions at baseline. Older age at NTZ start was the only significant risk factor for disease progression over long-term.
评估那他珠单抗（NTZ）的长期疗效，并确定人口统计学、临床和影像学预测因素，这些因素与全国性观察队列中≥7 年的长期疾病活动（≥7 年）有关，该队列使用前瞻性收集的真实数据。
我们分析了来自奥地利多发性硬化症治疗登记处（AMSTR）的 230 名患者的数据，这些患者自 2006 年以来任何时候都开始使用 NTZ 治疗，并且在没有超过三个月的治疗间隙的情况下至少使用 NTZ 治疗了 7 年。
在平均 9.3 年的治疗期间，估计平均每年的复发率（ARR）为 0.07。在 36 名（19%）患者中观察到持续 12 周的 EDSS 进展，在 31 名（16.3%）患者中观察到持续 24 周的 EDSS 进展。在 45 名（23.7%）和 42 名（22.1%）患者中观察到持续 12 周和 24 周的 EDSS 缓解。基线参数≥1 个钆增强 MRI 病变（发病率比（IRR）为 0.409（95%CI 0.283-0.593），p=0.001）、治疗前 12 个月 ARR≤1（发病率比（IRR）为 0.353（95%CI 0.200-0.623），p=0.001）和 EDSS≤1（发病率比（IRR）为 0.081（95%CI 0.011-0.581），p=0.012）与降低复发风险显著相关，而疾病持续时间≤5 年则显著增加了 ARR（发病率比（IRR）为 1.851（95%CI 1.249-2.743），p=0.002）。唯一预测 EDSS 进展（持续 12 周和 24 周）的基线参数是年龄>35 岁（HR 为 2.482（95%CI 1.110-5.549），p=0.027，HR 为 2.492（95%CI 1.039-5.978），p=0.041）。
这些真实数据显示，在使用 NTZ 治疗超过 7 年后，疾病的复发活动和疾病进展呈现稳定的病程。疾病活动的主要预测因素是治疗前更高的复发率、更高的残疾程度、更短的疾病持续时间和基线时缺乏钆增强 MRI 病变。NTZ 开始时年龄较大是长期疾病进展的唯一显著危险因素。
