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Objectives: To evaluate changes in gait and postural balance after D-ER withdrawal and reinitiation in people with MS with a clinical response to D-ER.
Methods: STEADY was an open-label, single-center study of D-ER Timed 25-foot Walk (T25FW) responders, defined as an investigator-determined improvement in T25FW between an off- and on-drug evaluation prior to study entry. Multiple gait and balance domains were measured using NeuroCom SMART™ Balance Master. On-drug evaluations were performed at screening and 1 week post-screening (baseline; 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). Balance parameters were the Sensory Organization Test, Adaptation Test, and Limits of Stability Test. An overall balance composite Z‑score, calculated as a weighted average of component Z‑scores, was a co-primary endpoint evaluated only if the gait outcome was significant. The Berg Balance Scale (BBS) was a secondary endpoint. A mixed-model ANOVA compared drug effects by treatment (on- vs off-drug). A similar analysis compared study periods. Tolerability was evaluated.
Results: 20 subjects (mean age 53.1 years, 60% female, 65% with relapsing remitting MS, mean time on D-ER of 315 days) enrolled and completed the study. Overall gait composite score was significant (p=.015) favoring treatment. The overall balance composite showed no treatment effect (p=.434), although there was progressive improvement in mean balance scores from Period 1 (51.9) to Period 2 (55.1) to Period 3 (61.1), which can be partly explained by a known learning effect. Improvement upon reinitiation was significant relative to Period 2 (p<.05). The BBS favored the on-drug periods (Periods 1 and 3 vs Period 2; p<.05), and comparing each on-drug period to the off-drug period; Period 1 vs Period 2 (p<.05), and Period 3 vs Period 2 (p<.05). D-ER was well tolerated.
Conclusions: There did not appear to be deterioration in overall balance during D-ER withdrawal, possibly due to a learning effect. Both learning and drug effects likely contributed to the significant improvement in balance upon D-ER reinitiation. BBS scores showed significant deterioration on D-ER withdrawal and significant improvement on reinitiation. Tolerability was consistent with previous studies.