Dalfampridine May Enhance the Effects of Physical Therapy on Gait in People with Multiple Sclerosis

Background: Dalfampridine extended-release (DER) can increase gait speed in people with multiple sclerosis (MS), but its therapeutic benefit occurs in only 38% of patients. Physical therapy (PT) can also improve gait speed in MS and may be a valuable adjunct to DER.

Objectives: To estimate the effect size of combining DER with PT on gait speed in people with MS, and to compare the effects to PT without DER.

Methods: 8 adults with MS and gait or balance difficulties were recruited: 4 newly prescribed DER and 4 not taking DER. Participants taking DER were evaluated prior to commencing the medication (week 0), then 3 weeks later to evaluate response to DER (week 3). Participants in the PT-only group completed the same assessments at the same time points. At week 3, all participants commenced PT, 2x/week for 6 weeks. PT consisted of functional strengthening, balance, gait, and dual-task training. The DER group continued taking DER for the study duration. Outcomes were reassessed after 6 weeks of PT (week 9) and again at 3-week follow up (week 12). The primary outcome was the Timed 25-foot Walk (T25FW; fast gait speed) at week 9. Secondary outcomes were self-selected gait speed, dual-task gait speed, and balance self-efficacy.

Results: All DER subjects were “non-responders” to DER at week 3 (<20% improvement in T25FW), with an average 12.8% (range: 5.8-19.4%) improvement in T25FW. T25FW improved from week 3-9 for the DER+PT group by 20.7% (95%CI: 3.8-37.6) and for the PT group by 6.8% (95%CI: 3.4-10.3). Although week 3-9 improvements were significant for both groups, the benefit was significantly greater for DER+PT (p=0.04). Mean week 0-9 increase for DER+PT was 30.5%, with all subjects surpassing the responder threshold of 20% (range: 20.5-48.9%). Self-selected and dual-task gait speed also increased significantly from week 3-9 for DER+PT by 0.15 m/s (SD 0.09) and 0.11 m/s (SD 0.07), respectively; improvements in the PT group and the between-group week 3-9 differences were not significant. Both groups improved significantly in balance confidence, but the change was significantly greater for DER+PT (p=0.003).

Conclusions: PT appears to enhance the effects of DER on gait in people with MS who do not reach the responder threshold for meaningful improvement on the drug alone. An alternate interpretation is that DER may enhance the effects of PT and exercise, since the benefits of PT were greater in those taking DER.