Fatigue, one of the most common symptoms in patients with multiple sclerosis (MS), impairs activity and limits physicial functioning in patients. A new patient reported outcome (PRO) instrument, the Fatigue Symptoms and Impact Questionnaire – Relapsing Multiple Sclerosis (FSIQ-RMS) has been developed with input from MS patients, to capture patient experience of MS related fatigue and addresses the limitations of existing fatigue instruments. The FSIQ-RMS is an MS specific, content-valid, concise instrument to assess symptoms relevant to MS and the impact of these symptoms on patients' lives.
The aim of this research was to establish a meaningful change threshold (MCT) for patients with MS associated fatigue on the FSIQ-RMS symptoms domain. Within-subject change of fatigue is critical for interpreting the individual effect of treatment on patients in terms of treatment response.
Data from the OPTIMUM study (NCT02425644) were obtained to derive MCT on the FSIQ-RMS symptoms domain score. The symptoms domain comprises seven items scored on an 11-point scale (0–10); with standardized domain score range from 0 to 100 with a higher score indicating greater fatigue. The Patient Global Impression of Severity of fatigue (PGI-S) assessed the patient’s fatigue severity on a 11-point Numeric Rating Scale from 0-10, anchored at 0 = “not severe at all” and 10 =”very severe”. The PGI-S was used as an anchor to establish and assess potential range of MCTs based on the magnitude of correlation between FSIQ-RMS symptoms domain score and PGI-S, and variability of change. Cumulative distribution function and kernel density plots (probability density functions [PDFs]) were also generated.
Correlation between the scales measuring change from baseline to end of treatment (Week 108) was above the acceptable threshold (0.35 [r=0.471]). Final analyses of the blinded OPTIMUM study data showed that an MCTof -6.3 points on the FSIQ-RMS symptom scale was equivalent to a 3-point improvement on the PGI-S, and captured all patients reporting improvement on the PGI-S without overlapping with patients reporting no change. The MCT of ‑6.3 points also exhibited a moderate effect size consistent with established guidelines.
Development of the MCT for the FSIQ-RMS provides an important metric to understand within patient improvement in fatigue symptoms using a PRO developed to specifically measure symptoms of MS fatigue.