Department of Neurology, MS Center Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands
Department of Neurology, MS Center Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
J Neurol Neurosurg Psychiatry. 2023 Oct;94(10):792-799. doi: 10.1136/jnnp-2022-330887. Epub 2023 May 12.
Focal inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS) diminishes with increasing age. Here we use patient-level data from randomised controlled trials (RCTs) of natalizumab treatment in RRMS to investigate the association of age and inflammatory disease activity.
We used patient-level data from the AFFIRM (natalizumab vs placebo in relapsing-remitting MS, NCT00027300) and SENTINEL (natalizumab plus interferon beta vs interferon beta in relapsing remitting MS, NCT00030966) RCTs. We determined the proportion of participants developing new T2 lesions, contrast-enhancing lesions (CELs) and relapses over 2 years of follow-up as a function of age, and investigated the association of age with time to first relapse using time-to-event analyses.
At baseline, there were no differences between age groups in T2 lesion volume and number of relapses in the year before inclusion. In SENTINEL, older participants had a significantly lower number of CELs. During both trials, the number of new CELs and the proportion of participants developing new CELs were significantly lower in older age groups. The number of new T2 lesions and the proportion of participants with any radiological disease activity during follow-up were also lower in older age groups, especially in the control arms.
Older age is associated with a lower prevalence and degree of focal inflammatory disease activity in treated and untreated RRMS. Our findings inform the design of RCTs, and suggest that patient age should be taken into consideration when deciding on immunomodulatory treatment in RRMS.
复发缓解型多发性硬化症（RRMS）的局灶性炎症疾病活动随年龄增长而减弱。本研究使用那他珠单抗治疗 RRMS 的随机对照试验（RCT）中的患者水平数据，调查年龄与炎症疾病活动之间的关联。
我们使用了 AFFIRM（RRMS 中纳他珠单抗与安慰剂对照，NCT00027300）和 SENTINEL（RRMS 中纳他珠单抗联合干扰素β与干扰素β对照，NCT00030966）RCT 的患者水平数据。我们确定了 2 年随访期间新 T2 病变、对比增强病变（CELs）和复发的参与者比例随年龄的变化，并使用时间事件分析研究年龄与首次复发时间的关联。
在基线时，年龄组之间 T2 病变体积和纳入前一年复发次数无差异。在 SENTINEL 中，年龄较大的参与者 CEL 数量明显较少。在两项试验中，新 CEL 数量和发生新 CEL 的参与者比例在年龄较大的组中显著较低。新 T2 病变数量和随访期间任何影像学疾病活动的参与者比例在年龄较大的组中也较低，尤其是在对照组中。
年龄较大与治疗和未治疗的 RRMS 中局灶性炎症疾病活动的发生率和严重程度较低相关。我们的发现为 RCT 设计提供了信息，并表明在决定 RRMS 的免疫调节治疗时应考虑患者年龄。
