Contributions
Abstract: P574
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Neuropsychology
Background: Dalfampridine extended release is a potassium‐channel blocker approved for improving walking in multiple sclerosis (MS). It has recently gained attention as a potential treatment for cognitive impairment, based on a few uncontrolled, observational studies. To date, data support that dalfampridine improves walking in MS, but there are no randomized controlled trials of its co-occurring effects on cognition.
Methods: Using a double‐blind, placebo-controlled, randomized, study design, 61 patients meeting revised McDonald criteria for MS were enrolled. All participants further met inclusion criteria for cognitive impairment, defined as a z < −1.5 on the Symbol Digit Modalities Test (SDMT). The active arm received 10mg of dalfampridine extended release, bid, and was compared to a placebo group. Excluded were patients receiving steroids in last thirty (30) days or a relapse in the last ninety (90) days prior to enrollment. An extensive battery of tests was administered at baseline and 3 months follow-up, including SDMT, Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test-II (CVLT2), Brief Visuospatial Memory Test-Revised (BVMTR), Delis-Kaplan Executive Function System-Sorting (DKEFS Sorting), Timed 25 Foot Walk (T25FW), and 9 Hole Peg Test (9HPT). Patient reported outcomes included the Beck Depression Inventory Fast Screen (BDI-FS) and the Fatigue Severity Scale (FSS). The effects of treatment were evaluated via mixed factor ANOVA.
Results: Treatment effects on the T25FW were replicated, with a Cohen"s d effect size of 0.27 for mean change in treatment vs. placebo. In contrast, there were no statistically significant interaction effects on cognitive function, fatigue or depression scores. Using a 20% change threshold, there were no significant interaction effects comparing responders vs. non-responders on any of the cognitive outcomes except PASAT, where responders had significant improvement relative to non-responders.
Conclusions: We confirm an effect of dalfampridine on timed ambulation in a placebo-controlled study. However, there were no effects on cognitive performance or self-report scales. Treated patients with a clinically meaningful improvement in ambulation had a benefit on auditory processing speed (PASAT), but no other change on cognitive or PRO outcomes. Thus, beneficial effects of dalfampridine on ambulation do not appear to be associated with gain in the other performance metrics examined.
Disclosure: This research was supported by an Acorda IIS.
Allison S. Drake has nothing to disclose.
Audrey Smerbeck has nothing to disclose.
Anjum Khan has nothing to disclose.
Margaret Bucello has received personal compensation for speaking and serving on advisory boards for Mallinckrodt, Biogen, Teva, Genzyme and Sanofi.
David Hojnacki has received personal compensation for consulting, speaking, and serving on scientific advisory boards for Biogen, Teva Neuroscience, EMD Serono, Genentech, and Genzyme/ Sanofi
Channa Kolb has received personal compensation for speaking and serving on a scientific advisory board for Biogen Idec, EMD Serono, Questcor, Novartis, Accorda and Teva.
Kara Patrick has nothing to disclose.
Bianca Weinstock-Guttman has received personal compensation for consulting, speaking and serving on scientific advisory boards for Biogen Idec, Teva Neuroscience, EMD Serono, Novartis, Questcor and Genzyme& Sanofi. She has received financial support for research activities from NMSS, NIH, ITN, Teva Neuroscience, Biogen Idec, EMD Serono, Aspreva, Novartis, Genzyme.
Robert Motl receives research support from Biogen, Acorda and Sun Health Technologies, provides consultation for Biogen and Acorda, and conducts CME for EMD Serono.
Ralph HB Benedict receives research support from Biogen, Novartis, Genzyme, Acorda and Mallinckrodt, provides consultation for Biogen, Genentech, Teva, Novartis, and Sanofi, and conducts CME for EMD Serono.
Abstract: P574
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Neuropsychology
Background: Dalfampridine extended release is a potassium‐channel blocker approved for improving walking in multiple sclerosis (MS). It has recently gained attention as a potential treatment for cognitive impairment, based on a few uncontrolled, observational studies. To date, data support that dalfampridine improves walking in MS, but there are no randomized controlled trials of its co-occurring effects on cognition.
Methods: Using a double‐blind, placebo-controlled, randomized, study design, 61 patients meeting revised McDonald criteria for MS were enrolled. All participants further met inclusion criteria for cognitive impairment, defined as a z < −1.5 on the Symbol Digit Modalities Test (SDMT). The active arm received 10mg of dalfampridine extended release, bid, and was compared to a placebo group. Excluded were patients receiving steroids in last thirty (30) days or a relapse in the last ninety (90) days prior to enrollment. An extensive battery of tests was administered at baseline and 3 months follow-up, including SDMT, Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test-II (CVLT2), Brief Visuospatial Memory Test-Revised (BVMTR), Delis-Kaplan Executive Function System-Sorting (DKEFS Sorting), Timed 25 Foot Walk (T25FW), and 9 Hole Peg Test (9HPT). Patient reported outcomes included the Beck Depression Inventory Fast Screen (BDI-FS) and the Fatigue Severity Scale (FSS). The effects of treatment were evaluated via mixed factor ANOVA.
Results: Treatment effects on the T25FW were replicated, with a Cohen"s d effect size of 0.27 for mean change in treatment vs. placebo. In contrast, there were no statistically significant interaction effects on cognitive function, fatigue or depression scores. Using a 20% change threshold, there were no significant interaction effects comparing responders vs. non-responders on any of the cognitive outcomes except PASAT, where responders had significant improvement relative to non-responders.
Conclusions: We confirm an effect of dalfampridine on timed ambulation in a placebo-controlled study. However, there were no effects on cognitive performance or self-report scales. Treated patients with a clinically meaningful improvement in ambulation had a benefit on auditory processing speed (PASAT), but no other change on cognitive or PRO outcomes. Thus, beneficial effects of dalfampridine on ambulation do not appear to be associated with gain in the other performance metrics examined.
Disclosure: This research was supported by an Acorda IIS.
Allison S. Drake has nothing to disclose.
Audrey Smerbeck has nothing to disclose.
Anjum Khan has nothing to disclose.
Margaret Bucello has received personal compensation for speaking and serving on advisory boards for Mallinckrodt, Biogen, Teva, Genzyme and Sanofi.
David Hojnacki has received personal compensation for consulting, speaking, and serving on scientific advisory boards for Biogen, Teva Neuroscience, EMD Serono, Genentech, and Genzyme/ Sanofi
Channa Kolb has received personal compensation for speaking and serving on a scientific advisory board for Biogen Idec, EMD Serono, Questcor, Novartis, Accorda and Teva.
Kara Patrick has nothing to disclose.
Bianca Weinstock-Guttman has received personal compensation for consulting, speaking and serving on scientific advisory boards for Biogen Idec, Teva Neuroscience, EMD Serono, Novartis, Questcor and Genzyme& Sanofi. She has received financial support for research activities from NMSS, NIH, ITN, Teva Neuroscience, Biogen Idec, EMD Serono, Aspreva, Novartis, Genzyme.
Robert Motl receives research support from Biogen, Acorda and Sun Health Technologies, provides consultation for Biogen and Acorda, and conducts CME for EMD Serono.
Ralph HB Benedict receives research support from Biogen, Novartis, Genzyme, Acorda and Mallinckrodt, provides consultation for Biogen, Genentech, Teva, Novartis, and Sanofi, and conducts CME for EMD Serono.