Frexalimab study validates PROMIS-Fatigue-MS-8a and MSIS-29v2 in relapsing multiple sclerosis patients

BACKGROUND: There are limited psychometric studies conducted using the Patient-Reported Outcomes Measurement Information System Adult Short Form-Fatigue-Multiple Sclerosis 8a (PROMIS-Fatigue-MS-8a) and Multiple Sclerosis Impact Scale-29 version 2 (MSIS-29v2) questionnaires. METHODS: Data were collected from a phase 2 trial (NCT04879628) investigating frexalimab in adults with relapsing multiple sclerosis (RMS). Reliability, convergent validity, construct validity, and sensitivity to change were assessed on PROMIS-Fatigue-MS-8a and MSIS-29v2 using Cronbach's alpha coefficient, intraclass correlation coefficient, Spearman's or polyserial correlation coefficients, analysis of variance, and analysis of covariance, respectively. Analyses were conducted using baseline and Week 12 data from pooled treatment arms. RESULTS: Item-to-item correlations were acceptable (0.4-0.9) for most of the items for both patient-reported outcomes (PROs) at baseline and Week 12. Internal consistency was excellent (Cronbach's alpha >0.90) for both PROs at baseline and Week 12. Additionally, good test-retest reliability was observed for PROMIS-Fatigue-MS-8a and the physical and psychological domains of MSIS-29v2. Convergent validity was supported by high correlations (r>0.50) between the PROMIS-Fatigue-MS-8a T-score and the MSIS-29v2 and the Patient Global Impression of Severity (PGIS)-Fatigue at baseline and Week 12. Construct validity was supported by significant differences between groups defined by the PGIS-Fatigue scores at baseline and Week 12 for both PROs (p<0.0001). Sensitivity to change was demonstrated by statistically significant differences in the mean change from baseline at Week 12 among groups defined by the PGIS-Fatigue and the Patient Global Impression of Change-Fatigue. CONCLUSIONS: PROMIS-Fatigue-MS-8a and MSIS-29v2 are valid and reliable measures for evaluating treatment benefits in clinical trials of RMS.