Eligible participants were randomized to receive either high- (n=52) or low-dose frexalimab (n=51), or matching placebos (n=12 and n=14, respectively) for 12 weeks. The Multiple Sclerosis Impact Scale 29 version 2 (MSIS-29v2) yields physical and psychological impact scores, with higher scores showing greater disability. Patient-Reported Outcomes Measurement Information System Short Form-Fatigue-Multiple Sclerosis 8a (PROMIS-Fatigue-MS-8a) is an 8-item patient questionnaire; higher T-scores indicate increased fatigue. Changes from baseline to W12 in scores were compared post hoc between groups using analyses of covariance. P-values were nominal.

At baseline, the pooled arms mean score (SD) for MSIS-29v2 physical and psychological impact subscales was 25.05 (23.05) and 34.55 (24.62), respectively, and PROMIS-Fatigue T-score was 52.68 (10.68). At W12, least-squares (LS) mean change (SE) in physical impact score was -1.52 (1.95) in high-dose, 0.43 (1.95) in low-dose, and 6.40 (2.79) in placebo, with high-dose showing significant improvement versus placebo (LS mean difference [95% CI]: -7.92 [-14.66, -1.18], P=0.021), and a numerical improvement in low-dose (-5.97 [-12.71, 0.77], P=0.082). The psychological impact scores between frexalimab and placebo groups showed no significant difference. PROMIS-Fatigue T-score, compared to placebo (LS mean change [SE]: 2.32 [1.37]), showed a significant improvement with both high-dose (LS mean change [SE]: -1.24 [0.96]; LS mean difference versus placebo [95% CI]: -3.55 [-6.86, -0.25], P=0.035) and low-dose (-1.41 [0.96]; -3.73 [-7.03, -0.43], P=0.027) frexalimab.

These preliminary findings suggest that frexalimab may improve physical impact and fatigue in people with RMS.