Dalfampridine for Mobility Limitations in People With Multiple Sclerosis May Be Augmented by Physical Therapy: A Non-randomized Two-Group Proof-of-Concept Pilot Study

Purpose: To demonstrate proof-of-concept for a combined physical therapy and pharmacological intervention and obtain preliminary estimates of the therapeutic efficacy of a motor-relearning physical therapy intervention with and without concurrent dalfampridine treatment on gait speed in people with mobility limitations due to multiple sclerosis (MS). Methods: Using a non-randomized, two-group design, 4 individuals with MS newly prescribed dalfampridine as part of their routine medical care, and 4 individuals with MS not taking dalfampridine completed a 3-week drug run-in or no-treatment baseline, respectively. After 3 weeks, all participants commenced physical therapy twice weekly for 6 weeks. Participants taking dalfampridine took the medication for the study duration. The physical therapy program comprised functional strengthening, gait training, balance training, and dual-task training. The primary outcome was Timed 25-foot Walk (T25FW) at the end of the 6-week physical therapy program. Results: For the 4 participants taking dalfampridine, average improvement in T25FW on drug only was 12.8% (95% CI 1.2 to 24.4%). During the 6-week physical therapy phase, both groups significantly improved T25FW, but the effect tended to favor the group taking dalfampridine (mean difference = −0.93 s, 95% CI −1.9 to 0.07 s, p = 0.064, d = 1.6). Whereas the physical therapy group had average T25FW improvement of 10.8% (95% CI 1.0 to 20.5%), the physical therapy plus dalfampridine group demonstrated average improvement of 20.7% (95% CI 3.8 to 37.6%). Conclusions: Further research is warranted to examine whether dalfampridine for mobility impairment may be augmented by physical therapy in people with MS.