To Örebro University

In a randomized open-label phase 3 trial in 62 children (1–12 years) with X-linked hypophosphatemia (XLH) (NCT 02915705), switching from conventional therapy (oral phosphate plus active vitamin D) to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved serum phosphate concentration, rickets, lower-extremity deformities, growth, mobility, and patient-reported outcomes (PROs) at 64 weeks. Children in Europe, USA, Canada, and Australia who completed 64 weeks’ treatment could continue to receive burosumab in the extension period (burosumab continuation group) or cross over from conventional therapy to burosumab (crossover group) to 124 weeks. A Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire was used in children aged ≥5 years to measure Pain Interference, Physical Function Mobility, and Fatigue; health-related quality of life was measured using the SF-10 Health Survey for Children (n=35). Here, we describe changes in PROs from baseline to weeks 64 and 88, and report whether the 3-point minimal important difference (MID) was reached for PROMIS domains (Thissen et al., 2016; PMID 26118768). The mean change from baseline exceeded the MID for Pain Interference at weeks 64 and 88 and for Fatigue at week 64 in the burosumab continuation group, and for Pain Interference and Fatigue at week 88 in the crossover group. Similar improvements in SF-10 Physical Health were seen baseline to week 64 in the burosumab continuation group, and week 64 to 88 in the cross-over group. SF-10 Psychosocial Health changed little in either group at the two timepoints.

Treatment with burosumab improved Pain Interference and Fatigue beyond the MID in children with XLH who switched from conventional therapy to receive 24 weeks of burosumab. Improvements were also maintained in children who received an additional 24 weeks’ burosumab treatment.