SPMS patients receiving siponimod (N=1099) or placebo (N=546) in the EXPAND study underwent SDMT at baseline and at 6-monthly intervals. A mixed-model repeated measures determined statistically significant group effects and a Cox proportional hazards model determined if these effects were clinically meaningful. “Sustained” change was defined as change from baseline by ≥4 points sustained on all subsequent assessments. Subgroup analyses were performed for patients with or without cognitive impairment at baseline (impaired SDMT <43; Drake et al 2018), and with a baseline SDMT ≥median or <median.

The proportion of patients with sustained improvement in SDMT was greater for siponimod versus placebo for patients with or without cognitive impairment at baseline, reaching significance for those without impairment (HR 1.49 [1.09,2.04]; p=0.0126), and for those with baseline SDMT ≥median and <median, reaching significance for those with baseline SDMT ≥median (HR 1.46 [1.10,1.95]; p=0.0094). Also, the proportion of patients with sustained deterioration was less with siponimod versus placebo for those with or without cognitive impairment, reaching significance for both groups: HR 0.72 ([0.53,0.96]; p=0.0269) and HR 0.76 ([0.58,1.00]; p=0.0477), respectively, and among those with baseline SDMT <median and ≥median, reaching significance for those with baseline SDMT <median (HR 0.65 [0.47,0.89]; p=0.0071).

Siponimod demonstrated significant functional benefits on CPS in SPMS patients, both for sustained improvement and against sustained deterioration in SDMT.