Over the course of treatment, in the placebo group, percent volume change from baseline to M24 of cGM was similar across all subgroups (−1.17 to −0.94); whereas for thalamus it differed (−3.56 to −1.31) and was more pronounced in subgroups ‘with gadolinium-lesion activity’ (−3.56), ‘active disease’ (−2.15), ‘age ≤45 years’ (−2.12), ‘disease duration ≤15 years’ (−2.09), and ‘SDMT score ≤43’ (−1.99). Across the subgroups studied, siponimod reduced cGM atrophy versus placebo by 48% to 116% (p<0.0001 at both M12 and M24; except for ‘with gadolinium-lesions’ p=0.0089 at M24) and thalamic atrophy by 30% to 68% (p<0.05 at both M12 and M24; except for ‘disease duration >15 years’ p=0.1029 at M12).