OBJECTIVES: XLH is a rare, life-long, often debilitating genetic disorder which causes rickets, lower extremity deformity, diminished growth, leading to physical function limitations, pain and fatigue. Valid PRO measures are required to evaluate the impact of treatment on patient-relevant outcomes. This study sought to evaluate the item/scale properties, reliability, validity, sensitivity to change of three PROMIS^® scales measuring Physical Function Mobility (Phy), Pain Interference (Pain), Fatigue (Ftg) in a small cohort paediatric XLH patients.

METHODS: Analyses were conducted using data (pooled across treatment groups) from a phase 3 multicenter, randomized, open label, active control study to evaluate the efficacy and safety of burosumab in XLH children aged 1-12years. PROMIS^® scales were completed for subjects ≥5yrs.

RESULTS: 35 patients, 45.7% female, mean age 8yrs (range 5-12yrs). Items on all 3 PROMIS^® scales showed some ceiling effects, all items met the convergent validity criterion (>0.40). All 3 scales had high internal consistency reliability (α=0.93). When the Six Minute Walk Test (6MWT) was used to define stability, intraclass correlations (ICCs) met the 0.70 threshold in all but one instance (Pain baseline-week 24). In known-groups analysis the PROMIS^® scales scores for sub-groups based on the RSS, 6MWT and RGI-C were not significantly different. There was weak-moderate support for convergent validity; stronger correlations with the 6MWT than the RSS or RGI-C. In responsiveness analyses, particularly when using the RGI-C to define groups, there was good support that the 3 scales are able to detect changes over time in an XLH paediatric population.

CONCLUSIONS: Analyses of this relatively small cohort provided encouraging support for the reliability, validity, and responsiveness of the PROMIS scales in paediatric patients with XLH, supporting their use to evaluate the effects of treatment interventions in clinical studies of XLH.