Effects of Fingolimod on Cognitive Status in Patients with Multiple Sclerosis: Prospective, Controlled Trial

Background: Cognitive impairment occurs in 40–65% of patients with multiple sclerosis (MS). Several clinical trials have shown beneficial effects of first line disease modifying therapies (DMTs) on cognitive measures in MS, but there has been no data regarding effects of fingolimod.

Objectives: The aim of the present study was to evaluate effect of fingolimod on cognitive function in MS.

Methods: The present study had a multi-center, examiner-blinded, controlled, prospective design. Adult relapsing remitting MS (RRMS) patients who initiated fingolimod treatment, with Expanded Disability Status Scale (EDSS) scores of 5.5 points or less enrolled in the study. To maintain treatment blinding, we used the two-physician principle: a treating neurologist was responsible for overall care of the patient; and an evaluating neurologist assessed patients at scheduled visits and performed cognitive tests, but was not otherwise involved in patient care. Neurological evaluations and cognitive tests were performed at baseline and every six month for 2 years. Age, sex and education-matched healthy control people were also evaluated cognitively at the same scheduled visits. For cognitive evaluation The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, which included the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-2 (CVLT2) and the Brief Visuospatial Memory Test-Revised (BVMT-R) used.

Results: A total of 96 patient (71 female, mean age: 34.4±7.3) and 98 healthy control (74 female, mean age: 33.8±8.4) included in the study. SDMT score improved at month 6 vs. baseline (39.25 vs. 42.45, p= 0.021. BVMTR score also improved at month 6 (24.35 vs. 26.2, p=0.017). CVLT2 improved from 48.3 to 50.95, p=0.012). 34 patients were found to be cognitively impaired at study entry on the basis of SDMT. At follow-up 22 patients were cognitively impaired (p=0.002). Number of cognitively impaired patients decreased from 36 to 27 on the basis of CVLT, and 33 to 19 on the basis of BVMTR at month 6. Patients were stable at month 12, month 18, and month 24.

Conclusions: This is the first study regarding effects of fingolimod in real life. The results of our study revealed a significant improvement in the cognitive function since sixth month of initiation of fingolimod in patients with RRMS.