OBJECTIVES: XLH is a rare genetic, lifelong, progressive bone disorder. Adults with XLH typically experience multiple symptoms including fatigue, bone and joint pain, and stiffness. A valid and reliable patient-reported outcome (PRO) measure is required to evaluate the impact of treatment on XLH-associated fatigue. This study evaluated the item/scale properties, reliability, validity, and sensitivity to change of the BFI in adults with XLH and established meaningful change/responder thresholds.

METHODS: Data from a Phase 3 multicenter, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of burosumab in adults with XLH (n = 134; 65% female; median [range] age 40 [18–65] years) were analysed.

RESULTS: Item responses were well distributed across the scale. Item-scale correlations were good for both Fatigue Interference (0.85–0.92) and Global Fatigue (0.72–0.90). In known-groups analysis, the BFI discriminated between groups differing in pain and 6-minute walk test (6MWT) distance, but not between those needing/not needing mobility assistance during the 6MWT. There was moderate support for convergent validity, with the strongest correlations with the BPI Pain Interference and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®) pain scores. Fatigue Interference and Global Fatigue both had high internal consistency reliability (α=0.94). When the Patient Global Impression of Improvement (PGI-I) was used to define stability, all intraclass coefficients indicated moderate or high test–retest reliability. Responsiveness analyses provided strong support that the BFI detects change over time when using the PGI-I to define change groups, but evidence was weaker when the 6MWT was used. Recommended responder thresholds were −1.5 for Worst Fatigue and −1.2 for Fatigue Interference and Global Fatigue.

CONCLUSIONS: These analyses confirm the reliability, validity, and responsiveness of the BFI in adults with XLH and provide responder thresholds supporting use of this PRO to evaluate the effects of treatment interventions in XLH clinical studies.