DX57
Improved Processing Speed on Fingolimod Therapy: Oral Symbol Digit Modalities Test Response in PREFERMS

Thursday, May 25, 2017
B2 (New Orleans Convention Center)
Ralph H Benedict, PhD , Department of Neurology, University at Buffalo, Buffalo, NY
Douglas L Arnold, MD , NeuroRx Research, Montreal, QC, Canada
Bruce AC Cree, MD, PhD , Neurology, University of California, San Francisco, CA
Xiangyi Meng, PhD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Lesley Schofield, PhD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Fernanda Boulos, MD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Nadia Tenenbaum, MD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
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Background: Cognitive decline is common in relapsing–remitting multiple sclerosis. Oral and written forms of the Symbol Digit Modalities Test (SDMT) can be used to assess cognitive function in multiple sclerosis. A clinically meaningful improvement in oral SDMT responses was seen in a subset of patients in PREFERMS.

Objectives: To understand how cognitive function improves with fingolimod treatment compared with injectable disease-modifying therapies (iDMTs) using the oral response version of the SDMT.

Methods: PREFERMSwas a 12-month, open-label, active-controlled, randomized, multicenter, phase 4 study. At enrollment, patients were either treatment-naïve or had received only one iDMT class (interferon or glatiramer acetate), and were randomized (1:1) to receive fingolimod 0.5 mg/day or a preselected iDMT. One on-study treatment switch was allowed after 3 months of therapy, or earlier if related to efficacy or safety. The mean change in SDMT score from baseline to last assessment on randomized treatment was compared between the two groups, and the proportions of patients with improvements in score of at least 3 or 4 were determined. The study was not powered to detect treatment differences in change in SDMT scores.

Results: The oral version of the SDMT was used in 73 patients receiving fingolimod and 65 receiving iDMTs (638 patients completed the written SDMT). Mean changes in oral SDMT score (95% confidence interval [CI]) were 3.4 (1.4, 5.4) in the fingolimod group and 0.3 (−1.8, 2.4) in the iDMT group. Increases in score of at least 3 and 4 were reported for 50.7% and 47.9% of patients receiving fingolimod, and for 38.5% and 33.8% of those receiving iDMTs, respectively. Respective between-group differences (95% CI) for SDMT score increases of at least 3 and 4 were 12.2% (−4.3%, 28.7%; p=0.1511) and 14.1% (−2.1%, 30.3%; p=0.0943), respectively.

Conclusions: Based on changes in oral SDMT scores in PREFERMS, there was a trend towards improved cognitive function in patients receiving fingolimod compared with those receiving iDMTs, and numerically more individuals receiving fingolimod than iDMTs reached clinically meaningful thresholds suggestive of cognitive improvement.