Effects Of Dalfampridine On Gait In Multiple Sclerosis: The Steady Study

Background: Dalfampridine extended release tablets (D-ER; prolonged-release fampridine in Europe) can improve walking in people with Multiple Sclerosis (MS).

Objectives: To evaluate gait and balance parameter changes in patients who had a clinical response to D-ER 10 mg twice daily using a therapy withdrawal and reinitiation design; the current analysis describes gait effects.

Methods: STEADY was an open-label, single-center study of D-ER Timed 25-foot Walk (T25FW) responders, defined as having an investigator-determined improvement in T25FW between an off- and on-drug evaluation prior to study entry. Gait parameters included Walk Across Test (WA), Tandem Walk Test (TW), and Step/Quick Turn Test (SQT). On-drug evaluations were performed at screening and 1 week post-screening (Period 1); D-ER withdrawal and off-drug evaluations, Days 5 and 11 (Period 2); and D-ER reinitiation and final on-drug evaluation, Day 15 (Period 3). An overall gait composite Z‑score was calculated as an average of component Z‑scores (primary endpoint). The T25FW and 2-Minute Walk test (2MW) were secondary endpoints. A mixed-model ANOVA compared effects while on-drug vs off-drug. A similar secondary analysis compared study periods.

Results: 20 subjects (mean age 53.1 years, 60% female, 65% with relapsing remitting MS, and mean time on D-ER of 315 days) enrolled and completed the study. On the WA, subjects did significantly better on step width, step length, and walking speed on-drug relative to off-drug (p<.05), consistent with on-drug improvements in secondary endpoints of T25FW (0.36 ft/sec; p<.001) and 2MWT (25.36 ft; p=.006). For the TW, although treatment effects were not significant, subjects walked faster in Period 3 vs. Period 2 (p<.05). The SQT was significantly better on-drug for both left and right turn sway but not for turn time. The composite Z-score showed that subjects did significantly better (p=0.015) on-drug (Periods 1 and 3) vs off-drug (Period 2). While overall gait deteriorated after D-ER withdrawal (Period 2 vs. Period 1), the difference was not significant; reinitiation (Period 3) resulted in a significant improvement (p<.05) vs. Period 2 (off-drug). D-ER was well tolerated.

Conclusions: D-ER withdrawal and reinitiation demonstrated that treatment has rapid, significant positive effects on a number of specific gait parameters, including walking speed, and distance. The tolerability profile was consistent with previous studies.