Combining PT With Dalfampridine In Patients With MS and Walking Limitations

Background:  Dalfampridine extended release tablets (D-ER; prolonged-release fampridine in Europe) are indicated to improve walking in patients with multiple sclerosis (MS), as demonstrated by an increase in walking speed in two Phase 3 clinical trials. Physical therapy (PT), particularly gait training, was also shown to improve walking performance in MS. The effects of combining D-ER with PT have not been studied.

Objectives: To evaluate the effect of combining PT with D-ER use on gait pattern compared to adding a home exercise program (HEP).

Methods: This was a single-blind, randomized, controlled, 2-arm cross-over study of ambulatory patients with MS and walking impairment (Ambulation Index score 2 to 6) taking D-ER, 10 mg twice daily. The setting was a neurorehabilitation clinic within an outpatient MS center. The intervention was a 4-week. bi-weekly outpatient PT intervention (stretching, strengthening, gait and balance training) versus 4-week home exercise program while continuing on D-ER. Each group crossed over to the other intervention after 4 weeks. The main outcome measures were the blinded evaluations: walking endurance (2-minute walk; 2MW), walking speed (Timed 25-foot Walk; T25FW), manual muscle testing (MMT), and spasticity (Modified Ashworth Scale; MAS). Other assessments included gait analysis (stride length, step width, double support time, Functional Ambulation Profile [FAP] score), Numeric Pain Rating Scale (NPRS), Patient Determined Disease Steps (PDDS), 12-Item MS Walking Scale (MSWS-12), and frequency of falls (self-report at screening; diary for other visits).       

Results: 21 subjects were enrolled and completed the study. There was a statistically significant improvement in 2MW with PT compared to HEP in both groups (PT-HEP 0.0025, HEP-PT 0.02). There were similar trends for the T25FW, but the difference did not reach statistical significance. A significant improvement in MMT scores was observed after PT in the PT-HEP group, but not in the other group. There was no significant change in MAS scores. No significant safety issues arose with PT or HEP.

Conclusions: Adding a 4-week PT intervention to D-ER use resulted in a significant improvement in walking performance on the 2MW, compared to a HEP. These findings support the rationale for referring to outpatient rehabilitation when prescribing D-ER to MS patients with walking limitations.