OBJECTIVES: Fabry disease (FD) is a rare genetic disorder due to deficiency of lysosomal enzyme, α-galactosidase-A. The Fabry Disease Patient-Reported Outcome (FD-PRO) instrument consists of 19 items that measure neuropathic symptoms (pain, tingling, numbness and burning in upper/lower extremities), headache, abdominal pain, heat intolerance, swelling, tinnitus, fatigue, hearing/vision impairment, hypohidrosis, and difficulty engaging in regular physical activities. Each item is evaluated on a 0 (no symptom) to 10 (symptom at its worst) numeric rating scale (NRS). In this study, we characterize the most bothersome symptoms (MBS) in FD, assess the severity of MBS using the FD-PRO, and quantify meaningful change – a useful metric to personalize patient-relevant endpoints.

METHODS: Participants with FD (n=66) were recruited via Fabry Support & Information Group for an online, cross-sectional survey. Participants completed the FD-PRO, identified their three MBS, and reported their minimal expectations for meaningful improvement in the MBS [henceforth referred to as minimal clinically important difference (MCID)].

RESULTS: Most participants were females (59%), with a mean age of 44 (±13) years, and 65% self-reported classic phenotype. Participants reported neuropathic pain in lower extremities (42%; median severity=7.0; interquartile range (IQR), Q1-Q3=4.5–9.0) and upper extremities (39%; median severity=6.5; IQR=5.0–7.0), and abdominal pain (27%; median severity=5.5; IQR=4.0–8.0) in their three MBS. On the 0-10 NRS, median and interquartile range (Q1–Q3) of MCID in MBS was reported as 3.0 (2.0–4.0), 2.0 (2.0–3.5), and 2.0 (1.0–3.0) for neuropathic pain in upper and lower extremities and abdominal pain, respectively.

CONCLUSIONS: Patient derived MCID for the three MBS was reported as IQR between 1 to 4 points on a NRS scale of 0 to 10. The study findings have implications in understanding the heterogeneity and presentation of symptoms in FD and interpreting the MCID of the FD-PRO in clinical studies.