OBJECTIVES: To validate the psychometric properties of version 2 of the Multiple Sclerosis Impact Scale 29 (MSIS-29v2) questionnaire in relapsing multiple sclerosis (RMS) patients.

METHODS: Psychometric and measurement properties of MSIS-29v2 were assessed using patient- data from the 12-week double-blind, randomized, placebo-controlled of the phase 2 study of frexalimab in adult RMS participants (NCT04879628; N=129). Two scores are derived from MSIS-29, the physical impact and the psychological impact subscale scores, both ranging from 0 to 100, higher score indicating worse disability. Item answer options on this version 2 range from 1 to 4 (eliminating level 5 “Quite a bite” included in version 1). Analyses were performed using baseline and Week 12 data from pooled treatment arms.

RESULTS: Item-to-item correlations were acceptable (i.e., between 0.4 and 0.9) for most items in each subscale at both visits. Excellent internal consistency (Cronbach’s alpha for both domains between 0.91 and 0.96, at baseline and Week 12) and adequate test-retest reliability (intraclass correlation coefficient ≥0.78 for physical domain, ≥0.66 for psychological domain, using Patient Global Impression of Change [PGIC-Fatigue] and Severity [PGIS-Fatigue]) was observed for both impact scores. Convergent validity was supported by high correlations with PROMIS-Fatigue MS-8a T-score (Patient Reported Outcome Measurement Information System (PROMIS))- and PGIS -Fatigue for both domains at baseline and Week 12. The construct validity was supported by significant differences among groups defined by PGIS-Fatigue at baseline and Week 12 (p <0.001) for both domains. Sensitivity to change was demonstrated by statistically significant differences in mean change from baseline for both impact scores at Week 12 among groups defined by PGIS-Fatigue and PGIC-Fatigue.

CONCLUSIONS: Both subscales showed robust measurement properties in this phase 2 clinical study, indicating that MSIS-29v2 can be a valuable outcome measure in evaluating physical and psychological impact in adult RMS patients.