OBJECTIVES: XLH is a rare inherited bone disorder causing pain due to multiple factors e.g. skeletal deformity, osteoarthritis, pseudofractures, fractures and enthesopathy. A valid and reliable PRO measure is required to evaluate the impact of treatment on XLH-associated pain. This study sought to confirm an initial evaluation of the item/scale properties, reliability, validity, sensitivity to change of the BPI-SF in adult XLH patients, and to establish meaningful change/responder thresholds.

METHODS: Analyses were conducted using data (pooled across treatment groups) from a phase 3 multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of burosumab in adults with XLH.

RESULTS: 134 patients, 64.9% female, mean age 40.0 (range 18-65 yrs). Item response distributions were well distributed across the response scale. Item-scale correlations ranged from 0.61-0.81. In known-groups analysis the BPI-SF could discriminate between groups differing in baseline: pain medication use, use of walking device, pain severity and walking ability. There was moderate support for convergent validity with stronger correlations with the Patient Global Impression of Severity (PGI-S) than the six-minute walk test (6MWT). The BPI-SF Pain Interference dimension had very high internal consistency reliability (α=0.917). When the PGI-I was used to define stability, all ICCs were indicative of either moderate or high test-retest reliability. In responsiveness analyses, particularly when using the PGI-I to define change groups, there was strong support that the BPI-SF domain scores are able to detect changes over time in this population. For the Worst Pain item, a change score of 1.72 is recommended as a threshold for defining responders, and a change score of 1.0 for the Pain Interference score.

CONCLUSIONS: Analyses support the reliability, validity, and responsiveness of the BPI-SF in adult XLH patients and provide responder thresholds, supporting the use of this PRO to evaluate the effects of treatment interventions in clinical studies.