Cognitive Evolution in Tysabri (natalizumab) Treated Multiple Sclerosis Patients

Thursday, May 29, 2014
Trinity Exhibit Hall
Francois H Jacques, M.D. , Clinique Neuro-Outaouais, Gatineau, QC, Canada
Brian T Harel, PhD , Yale Child Study Center, New Haven, CT
Adrian J Schembri, DPsych , Cogstate, Melbourne, Australia
Chantal Paquette, BScN , Clinique Neuro-Outaouais, Gatineau, QC, Canada
Joanne S Gale, Dphil , Cogstate, Melbourne, Australia
Brigitte Bilodeau, BSc , Clinique Neuro-Outaouais, Gatineau, QC, Canada


Cognitive dysfunction affects 40-60% of MS patients and progresses over time.

Natalizumab has shown to be superior to placebo in preserving cognitive function for the first two

years of therapy.


The objectives are to understand the impact of natalizumab on cognition beyond

two years of therapy and investigate whether baseline characteristics are predictive of clinical



This is a single-center, 24-month, observational study. Sixty-three patients treated with

natalizumab were assessed prior to monthly infusions using the Cogstate battery and SDMT. The

Beck depression questionnaire was also administered at baseline and every 4th month prior to

infusion. Patient demographics, MS treatment history, EDSS, MSSS, and natalizumab treatment

duration were collected at baseline. Patients with cognitive impairment from other causes were

excluded. A linear mixed model was conducted with time on natalizumab (4 years, n=12) as a

between-subjects factor, time point as a within-subjects factor, and age, EDSS, type of MS and

number of prior drug treatments as covariates. The current data are from the 12-month interim



Irrespective of time on natalizumab, significant improvements were observed in executive

function (p< .0001), verbal memory (p< .0001), and working memory (p< .0001), whereas

processing speed (p=.19) and attention (p=.15) remained unchanged. Only one patient had clinically

meaningful decline, defined as a decline of 1 or more standard deviations over three consecutive

months on two or more Cogstate tests.


Interim analysis suggests that natalizumab can preserve cognitive function and the

ability to learn beyond two years of continuous therapy.