Cognitive functioning following one-year natalizumab treatment: A non-randomized clinical trial

Cognitive impairment is common in multiple sclerosis (MS) and can have serious impact on social and occupational functioning. Natalizumab reduces relapse rates, magnetic resonance imaging (MRI) lesions, and progression of disability. Previous studies on cognitive functioning have not based inclusion on cognitive performance criteria. The aim of the present study was to determine any potential natalizumab-related cognitive effects on MS patients performing below normal limits on neuropsychological testing.

Patients starting natalizumab (n = 21) and a quasi-control group of stable MS patients (n = 13) on first line disease modifying treatment were included following neuropsychological assessment demonstrating subnormal cognitive performance. Assessment, using ten cognitive variables, was repeated after 12 months. Symptoms of fatigue, anxiety and depression were also examined. Raw scores on the cognitive tests were transformed into Z-scores based on published age-corrected normative data.

Between-group analyses on difference Z-scores (baseline - follow-up) yielded significant results on Paced Auditory Serial Addition Test-2 (PASAT-2) (P = .008), with the natalizumab group showing larger improvement than quasi control patients. On PASAT-2, 28,5% from the natalizumab group demonstrated >1 SD improvement, indicative of clinically meaningful change, compared with none in the quasi control group. Patients receiving natalizumab showed within-group improvements on six of the ten cognitive variables. There were no group differences in symptoms of fatigue, anxiety or depression.

The results demonstrate improvement in information processing speed following 12-months of natalizumab treatment. The results are interpreted as reflection of anti-inflammatory properties of natalizumab rather than retest- or long-term restorative effects.