Cognitive evolution in natalizumab-treated multiple sclerosis patients

Abstract

Background: Cognitive dysfunction affects up to 65% of multiple sclerosis (MS) patients and progresses over time. Natalizumab has been shown to be superior to placebo in preserving cognition for the first two years of therapy.

Objectives: The objectives of this study are to understand the impact of natalizumab on cognition beyond two years of therapy and to investigate whether baseline characteristics are predictive of clinical response.

Methods: This is a single-center, 24-month, observational study. Sixty-three patients treated with natalizumab were assessed prior to monthly infusions using a Cogstate battery and the Symbol Digit Modalities Test (SDMT). Patient demographics were collected at baseline. A linear mixed model was conducted with duration of natalizumab therapy as a between-subjects factor (≤2 or >2 years), assessment as a within-subjects factor, and Multiple Sclerosis Severity Score (MSSS) as a covariate.

Results: Aside from the MSSS (p = 0.0074), the two groups were identical. No patient showed evidence of sustained cognitive deterioration over the 24-month period. Baseline parameters including impaired cognition did not influence the trajectory of cognitive change over 24 months.

Conclusions: Our results suggest that natalizumab preserves cognition following four to seven years of continuous therapy. This occurs irrespective of baseline characteristics, including impaired cognition.

Keywords: Cognition; multiple sclerosis; natalizumab; relapsing–remitting.

Figure 1.

The mean score of patients having received less than two years of natalizumab compared to those with more than two years of natalizumab treatment on the International Shopping List Task.

Figure 2.

Change in performance on the Groton Maze Learning Test in those patients having received less than two years of natalizumab versus those with greater than two years of natalizumab treatment.

Figure 3.

Change in performance on the Symbol Digit Modalities Test (SDMT). Performance on the SDMT between patients having received less than two years of natalizumab compared with those with more than two years of natalizumab treatment.

Figure 4.

Change in performance on the Symbol Digit Modalities Test (SDMT) for patients with and without impaired cognition at baseline. Performance on the SDMT between patients with impaired cognition at baseline (red line) and those who were not impaired (gray line).