晚发和成人复发缓解型多发性硬化症患者在使用疾病改良疗法方面的差异

摘要(中文译文)

对于晚发型多发性硬化（LOMS）且呈复发-缓解起病的患者，其治疗策略仍不明确，可能导致与成人起病型多发性硬化（AOMS）相比，疾病修正治疗（DMT）的暴露不足。我们在法国多发性硬化登记数据库中，于疾病严重程度可比的条件下，研究了LOMS与AOMS之间DMT使用情况的差异。这项回顾性队列研究使用了2024年12月从法国多发性硬化登记数据库中提取的数据，纳入1997年至2023年间复发-缓解起病的多发性硬化患者。主要结局为按多发性硬化起病年龄计算的年度接受DMT的概率，并针对疾病严重程度进行调整。次要结局包括年度接受高效DMT（HEDMT）的概率、分别接受每种DMT的概率、至少有1次EDSS测量的概率、至少有1次脑MRI的概率，以及DMT的启动和停用情况。我们使用了带有广义估计方程的纵向logistic模型和逆删失概率加权。共纳入36,148例患者；26,540例（73.4%）为女性，平均年龄为33.5岁（标准差，9.7），2,308例（6.4%）在起病时年龄≥50岁。中位随访时间为10.8年（四分位距，5.6-17.0）。与AOMS患者相比，LOMS患者年度接受DMT的概率较低（73.7% vs 83.1%；比值比[OR]，0.57 [95% CI 0.52-0.62]）。HEDMT的差异更大（24.6% vs 44.4%；OR，0.41 [95% CI 0.36-0.46]）。LOMS患者更可能接受特立氟胺，而较少接受富马酸酯类、S1PR调节剂、那他珠单抗或抗CD20药物。LOMS与AOMS患者之间的临床和影像学随访无显著差异。LOMS患者的DMT启动率较低（每患者年0.13 vs 0.17次启动）。尽管DMT停用比例相似（59.7% vs 60.4%，排除妊娠相关停用），但在LOMS患者中，这些停用更常归因于完全停用策略（27.9% vs 22.3%），而较少归因于升级策略（9.2% vs 13.8%）。在疾病严重程度可比的条件下，LOMS患者接受DMT治疗的可能性低于AOMS患者，尤其是HEDMT。这一差距既由较少的DMT启动所驱动，也由更频繁的完全停用所驱动。

Abstract

The therapeutic strategy for late-onset multiple sclerosis (LOMS) with a relapsing-remitting onset remains unclear, potentially leading to underexposure to disease-modifying therapies (DMTs) compared with adult-onset multiple sclerosis (AOMS). We investigated the differences in DMT use between LOMS and AOMS within the French MS registry at comparable levels of disease severity. This retrospective cohort study used data extracted in December 2024 from the French MS registry on patients with relapsing-remitting onset MS between 1997 and 2023. The primary outcome was the annual probability of receiving a DMT according to age at MS onset, adjusted for disease severity. Secondary outcomes included the annual probability of receiving a highly effective DMT (HEDMT), each DMT separately, having ≥1 EDSS measurement, having ≥1 brain MRI, and DMT initiations and discontinuations. We used a longitudinal logistic model with generalized estimating equations and an inverse-probability-of-censoring weighting. A total of 36,148 were included patients; 26,540 (73.4%) were female, mean age was 33.5 years (SD, 9.7), and 2,308 (6.4%) were aged ≥50 at disease onset. Median follow-up was 10.8 years (interquartile range, 5.6-17.0). Patients with LOMS had a lower annual probability of receiving a DMT compared with patients with AOMS (73.7% vs 83.1%; odds ratio [OR], 0.57 [95% CI 0.52-0.62]). The difference was greater for HEDMT (24.6% vs 44.4%; OR, 0.41 [95% CI 0.36-0.46]). Patients with LOMS were more likely to receive teriflunomide and less likely to receive fumarates, S1PR modulators, natalizumab, or anti-CD20. Clinical and radiologic follow-up did not differ significantly between patients with LOMS and AOMS. The rate of DMT initiation was lower in patients with LOMS (0.13 vs 0.17 initiation per patient-year). Although the proportions of DMT discontinuation were similar (59.7% vs 60.4%, excluding pregnancy-related discontinuations), these discontinuations were more often attributed to a complete discontinuation strategy (27.9% vs 22.3%) and less often to an escalation strategy (9.2% vs 13.8%) in patients with LOMS. At comparable levels of disease severity, patients with LOMS were less likely to be treated with DMTs, particularly HEDMT, than patients with AOMS. This gap was driven both by fewer DMT initiations and more frequent complete discontinuations.

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