Evaluation of functional outcome measures after fampridine treatment in patients with multiple sclerosis - An interventional follow-up study

Abstract

Objective: The purpose of this interventional study on participants with multiple sclerosis (MS) with walking disability was to evaluate changes in functional hand and walking measurements after fampridine treatment, after stratifying by the Expanded Disability Status Scale (EDSS). We furthermore wanted to investigate different functional measurements to evaluate their ability to detect responders to fampridine with a clinically relevant improvement.

Methods: Patients were recruited from the MS Clinic at Odense University Hospital and were classified into two disability groups based on their EDSS score (moderate EDSS (EDSS_Mod) 4.5-5.5 [n = 19] and severe EDSS (EDSS_Sev) 6.0-7.0 [n = 14]). At baseline (visit 1) they completed the Timed 25-Foot Walk (T25FW), 2-Minute Walk Test (2MWT), Nine Hold Peg Test (9HPT), 12-item Multiple Sclerosis Walking Scale (MSWS-12), and the Six Spot Step Test (SSST). Participants were given 10 mg twice daily fampridine for 14 days before retested (visit 2). For each measurement, cut-off values were used to define responders with a clinically relevant improvement to treatment. The measurements were evaluated separately and in combination.

Results: Of the 33 participants, 25 (75.8%) were identified as having a clinically relevant improvement (CRI). For all patients combined (EDSS_All), all five measurements showed significant functional improvement after treatment. For the individual measurements, the highest participant response rates after 14 days of fampridine treatment were seen on the MSWS-12 (57.6%) and 2MWT (42.4%). The 2MWT also showed the largest performance improvement (18.5%) from visit 1 to visit 2. For patients with severe disability (EDSS_Sev), no significant improvement was seen after fampridine treatment on the T25FW, and most of the responders to T25FW had moderate disability (EDSS_Mod, 71.5%). Conversely for the SSST, most responders were EDSS_Sev (83.3%). No participants had a clinically relevant improvement on the 9HPT. The combination of T25FW, SSST, and MSWS-12 was less sensitive in distinguishing responders from non-responders, whereas the combination of 2MWT and MSWS-12 identified the same responders and could better distinguish fampridine responders from non-responders.

Conclusion: EDSS level did not influence the effect of fampridine treatment on functional hand and walking measures and the responsiveness of the measurements differed only a little between moderate and severe EDSS levels. The combination of self-reported walking capacity (MSWS-12) and walking endurance (2MWT) was better than T25FW, SSST, and MSWS-12 at detecting clinically meaningful improvement after fampridine treatment, which could prove useful in the clinical monitoring of walking disabilities in MS during fampridine treatment.

Keywords: 2-minute walk test; 4-aminopyridine; Clinically meaningful improvement; EDSS; Multiple sclerosis; Subjective outcome; Walking measures.