Four-Year Expanded Disability Status Scale Outcomes in Patients Treated with Fingolimod in the Phase 3 and Extension Trial Program

Background: Assessment of long-term disability status is important for characterizing the benefit–risk profile of disease-modifying therapies (DMTs) in multiple sclerosis (MS), although a lack of control group and selective drop-outs may produce bias.

Objectives: To evaluate Expanded Disability Status Scale (EDSS) scores over time in patients with relapsing forms of MS who were treated with fingolimod in the phase 3 FREEDOMS, FREEDOMS II, and TRANSFORMS studies and their extensions.

Methods: EDSS data from patients initiating fingolimod in the phase 3 core or extension studies were pooled for post hocanalysis. Kaplan–Meier estimates of the proportions of patients not reaching EDSS scores 4, 6, and 7 during fingolimod treatment were calculated for patients who received fingolimod 0.5 mg and those who received fingolimod at any dose. A descriptive analysis is provided for the proportions of patients at 24, 36, and 48 months with an EDSS score less than or equal to the score at fingolimod treatment initiation.

Results: Mean and median treatment exposure were 920 days and 967 days in patients receiving fingolimod 0.5 mg (n = 1641) and 882 days and 918 days in those receiving all fingolimod doses (n = 3283). Kaplan–Meier estimates of proportions of patients not reaching EDSS scores 4, 6, and 7 were 71.3%, 87.8%, and 96.7% for fingolimod 0.5 mg and 69.5%, 87.0%, and 96.3% for all fingolimod doses, respectively. At month 24, month 36 and month 48 the proportions of patients with EDSS score less than or equal to the baseline value were 67.9% (n = 1324), 64.7% (n = 909), and 66.8% (n = 587) for fingolimod 0.5 mg and 69.0% (n = 2580), 66.4% (n = 1727), and 66.2% (n = 1110) for all fingolimod doses. Of these, EDSS was improved at months 24, 36, and 48 compared with the baseline value in 15.7%, 17.4%, and 17.4% of patients treated with fingolimod 0.5 mg, and 17.5%, 18.7%, and 18.5% of those receiving all fingolimod doses.

Conclusions: Most patients treated with fingolimod for up to 4.9 years remained free of the need for walking assistance. Approximately two-thirds of patients who continued fingolimod treatment had the same or a better EDSS score after 2, 3, and 4 years of treatment, of which 16–18% showed improvement. Absence of a control group and selective drop-outs may bias these results.