Patient-Reported Outcomes from a Randomized, Active-Controlled, Open-Label, Phase 3 Trial of Burosumab Versus Conventional Therapy in Children with X-Linked Hypophosphatemia

Abstract

Changing to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved phosphorus homeostasis, rickets, lower-extremity deformities, mobility, and growth versus continuing oral phosphate and active vitamin D (conventional therapy) in a randomized, open-label, phase 3 trial involving children aged 1-12 years with X-linked hypophosphatemia. Patients were randomized (1:1) to subcutaneous burosumab or to continue conventional therapy. We present patient-reported outcomes (PROs) from this trial for children aged ≥ 5 years at screening (n = 35), using a Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-10 Health Survey for Children. PROMIS pain interference, physical function mobility, and fatigue scores improved from baseline with burosumab at weeks 40 and 64, but changed little with continued conventional therapy. Pain interference scores differed significantly between groups at week 40 (- 5.02, 95% CI - 9.29 to - 0.75; p = 0.0212) but not at week 64. Between-group differences were not significant at either week for physical function mobility or fatigue. Reductions in PROMIS pain interference and fatigue scores from baseline were clinically meaningful with burosumab at weeks 40 and 64 but not with conventional therapy. SF-10 physical health scores (PHS-10) improved significantly with burosumab at week 40 (least-squares mean [standard error] + 5.98 [1.79]; p = 0.0008) and week 64 (+ 5.93 [1.88]; p = 0.0016) but not with conventional therapy (between-treatment differences were nonsignificant). In conclusion, changing to burosumab improved PRO measures, with statistically significant differences in PROMIS pain interference at week 40 versus continuing with conventional therapy and in PHS-10 at weeks 40 and 64 versus baseline.Trial registration: ClinicalTrials.gov NCT02915705.

Keywords: Burosumab; Patient-reported outcomes; Patient-reported outcomes measurement information system; X-linked hypophosphatemia.

Fig. 1

Baseline PROMIS (a) pain interference, (b) physical function mobility, and (c) fatigue scores for patients aged ≥ 5 years (n = 35). Data show standardized PROMIS T-scores; higher T-scores indicate more pain interference, better function mobility, and worse fatigue. Reference lines at ± 1 SD of the mean are based on a population mean of 50 and SD of 10. PROMIS Patient-Reported Outcomes Measurement Information System, SD standard deviation

Fig. 2

Change from baseline in PROMIS (a) pain interference, (b) physical function mobility, and (c) fatigue scores for patients aged ≥ 5 years (n = 35). Data are expressed as LS mean (standard error). *p < 0.05 for LS mean change at week 40 (burosumab–conventional therapy). ^†Indicates the mean change is ≥ 3-point MID from baseline. LS least-squares, MID minimally important difference, PROMIS Patient-Reported Outcomes Measurement Information System

Fig. 3

Baseline SF-10 Health Survey for Children (a) PHS-10 and (b) PSS-10 for patients aged ≥ 5 years (n = 35). P.25, P.50, and P.75 are the 25th, 50th, and 75th percentiles from the general population. Higher global scores indicate better HRQoL. HRQoL health-related quality of life, PHS-10 physical health score, PSS-10 psychosocial health score, SF-10 Short Form-10

Fig. 4

Changes from baseline to weeks 40 and 64 for SF-10 Health Survey for Children (a) PHS-10 and (b) PSS-10 for all patients aged ≥ 5 years (n = 35). Data are expressed as LS mean ± standard error. *p < 0.01 for change from baseline to week 64; **p < 0.001 for change from baseline to week 40. LS least-squares, PHS-10 physical health score, PSS-10 psychosocial health score, SF-10 Short Form-10