Effects of Fingolimod on Categorical Change in T2 Lesion Volume and Clinical Outcomes in Patients with Relapsing–Remitting Multiple Sclerosis

Background: Clinical evidence from patients with relapsing–remitting multiple sclerosis (RRMS) suggests an association between change in T2 lesion volume (LV) and confirmed disability progression (CDP).

Objectives: To investigate the association between categorical change in T2 LV and clinical outcomes in the FREEDOMS study and extension.

Methods: This study performed post hoc analyses of T2 LV at baseline and month 24 in patients who received fingolimod 0.5 mg or placebo. Categorical subgroups were defined according to change in T2 LV from baseline to month 24: decreased (< –500 mm³); stable (≥ –500 mm³ and ≤ 500 mm³); and increased (>500 mm³). Clinical outcomes included 3- and 6-month CDP measured by mean change in Expanded Disability Status Scale (EDSS) score and multiple sclerosis functional composite (MSFC) z-scores. Additional analyses assessed the relationship between LV change in the first 2 years and disability through month 48.

Results: A total of 1057 of 1272 patients had T2 LV assessments at baseline and month 24. At month 24, the proportions with decreased, stable, and increased T2 LV were 15.5% (n = 164), 59.9% (n = 633), and 24.6% (n = 260), respectively. A greater proportion of patients treated with fingolimod 0.5 mg had decreased or stable LV than those receiving placebo (decreased: 17.7% versus 5.8%; stable: 67.5% versus 50.3%; increased: 14.8% versus 40.3%). In the overall population, increased LV was associated with worsening disability at month 24 (LV decreased; stable; increased: changes in EDSS score [−0.01; −0.01; 0.14] and MSFC score [0.08; 0.01; −0.08]; and proportions with 3-month CDP [16.4%; 17.4%; 21.7%] and 6-month CDP [11.3%; 14.0%; 19.0%]). The results within the fingolimod and placebo groups were consistent with this overall pattern, and LV in the first 2 years was similarly associated with disability at month 48.

Conclusions: Categorical change in T2 LV in the first 2 years was associated with disability at months 24 and 48 in patients with RRMS. Patients with increased T2 LV exhibited higher mean changes in EDSS and MSFC scores and a shorter time to CDP. Fewer patients receiving fingolimod had increased T2 LV, and higher proportions demonstrated stable or decreased LV, compared with those receiving placebo.