OBJECTIVES: Fatigue is the most common symptom in patients with multiple sclerosis (MS). We aimed to establish a meaningful change threshold for the symptom domain of the FSIQ-RMS, a new patient-reported outcome (PRO) instrument.

METHODS: Data from OPTIMUM study (NCT02425644) were used to derive a meaningful change threshold in the FSIQ-RMS symptoms scale. The FSIQ-RMS measures fatigue-related symptoms and their impact on patients with MS. The symptoms domain comprises seven items scored on an 11-point scale (0–10; total score range standardized 0-100) higher scores representing greater fatigue. A patient’s global impression of severity of fatigue scale (PGI-S) scored by the subject on an 11-point numeric rating scale ranging from 0 to 10 was used as a prospective anchor to establish and assess a potential range for a meaningful change threshold. Correlation between the scales measuring change from baseline to end of treatment (Week 108) was acceptable (0.35 [r=0.471]), suggesting the PGI-S is a suitable anchor for patient-reported fatigue.

RESULTS: Both uncollapsed and collapsed change on the PGI-S were used to detect improvement on the FSIQ-RMS symptom scale. For patients who report a 3‑category improvement, a mean change of -6.3 (median change -7.1; confidence interval -9.97, -2.57), statistically significant (p=0.0014), had a moderate effect (SES=0.52). Overall, the data suggested that a 3-category improvement on the PGI-S was necessary to reach a threshold for determining a meaningful change on the FSIQ-RMS symptom scale. Therefore, a meaningful change threshold of -6.3 (based on the mean value of the 3-category improvement on the uncollapsed data) points was considered appropriate in this population.

CONCLUSIONS: The FSIQ-RMS, an MS-specific fatigue scale was developed according to the FDA’s PRO Guidelines. Identification of its meaningful change threshold, enables interpretation of data required to measure and track symptoms of MS-associated fatigue.