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Background <p>Cognitive impairment is a common feature of multiple sclerosis (MS), affecting daily functioning and quality of life. We aimed to investigate how disease-modifying therapies (DMTs) of varying efficacy are associated with long-term cognitive trajectories in MS, as measured by the Symbol Digit Modalities Test (SDMT).</p> Methods <p>Using the data from Swedish population-based MS cohorts linked to the Swedish MS registry, we included individuals with relapsing-onset MS receiving DMT to evaluate longitudinal SDMT trajectories. From a cohort of 5467 treated individuals, several analytic subsets were defined for specific trajectory analyses. Mixed-effects models were used to examine changes in cognitive performance across treatment categories, including platform therapies, high-efficacy therapies overall, and specific high-efficacy agents.</p> Results <p>SDMT scores increased during the first years of follow-up among individuals initiating high-efficacy DMT and subsequently declined, whereas changes in the platform group were smaller over time. Differences between groups were observed at years 3 and 4, with an estimated difference of approximately 2 points, which were not sustained at later follow-up. When compared with anti-CD20 therapies, natalizumab-treated individuals showed a greater early increase (<i>β</i> −&#xa0;0.77, 95% CI −&#xa0;1.26, −&#xa0;0.27) and a more pronounced subsequent decline (<i>β</i> 0.38, 95% CI 0.21–0.55), with trajectories converging over time. Adjustment for repeated testing attenuated early increases in SDMT scores.</p> Conclusions <p>There was limited evidence for a sustained or clinically relevant short-term effect of high-efficacy DMTs on cognitive trajectories in MS. Differences between groups and changes over time are likely influenced by underlying patient characteristics and practice effects related to repeated testing.</p>

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Trajectories of processing speed in multiple sclerosis across disease-modifying therapies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月20日

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  • Jie Guo,
  • Eva Johansson,
  • Jan Hillert,
  • Tomas Olsson,
  • Lars Alfredsson,
  • Anna Karin Hedström

摘要

Background

Cognitive impairment is a common feature of multiple sclerosis (MS), affecting daily functioning and quality of life. We aimed to investigate how disease-modifying therapies (DMTs) of varying efficacy are associated with long-term cognitive trajectories in MS, as measured by the Symbol Digit Modalities Test (SDMT).

Methods

Using the data from Swedish population-based MS cohorts linked to the Swedish MS registry, we included individuals with relapsing-onset MS receiving DMT to evaluate longitudinal SDMT trajectories. From a cohort of 5467 treated individuals, several analytic subsets were defined for specific trajectory analyses. Mixed-effects models were used to examine changes in cognitive performance across treatment categories, including platform therapies, high-efficacy therapies overall, and specific high-efficacy agents.

Results

SDMT scores increased during the first years of follow-up among individuals initiating high-efficacy DMT and subsequently declined, whereas changes in the platform group were smaller over time. Differences between groups were observed at years 3 and 4, with an estimated difference of approximately 2 points, which were not sustained at later follow-up. When compared with anti-CD20 therapies, natalizumab-treated individuals showed a greater early increase (β − 0.77, 95% CI − 1.26, − 0.27) and a more pronounced subsequent decline (β 0.38, 95% CI 0.21–0.55), with trajectories converging over time. Adjustment for repeated testing attenuated early increases in SDMT scores.

Conclusions

There was limited evidence for a sustained or clinically relevant short-term effect of high-efficacy DMTs on cognitive trajectories in MS. Differences between groups and changes over time are likely influenced by underlying patient characteristics and practice effects related to repeated testing.