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

Health-related Quality of Life and Direct Healthcare Costs of X-linked Hypophosphatemia in Spain

“…For caregivers and parents, the EQ-5D-5L index was 0.821 ± 0.157 and the VAS score was 75.47 ± 17.24. These values were slightly lower than those found in the general Spanish population: 0.914 ± 0.15 and 77.53 ± 18.60, respectively [14].…”

“…In clinical studies in children [13,43,44] and adults [45][46][47] with XLH, burosumab increased phosphatemia, improved growth and deformities in children, improved physical function, and relieved pain. Moreover, it enhanced HRQoL after 48 and 64 months of therapy, respectively in adults [45][46][47] and children [14].…”

“…There are few studies related to HRQoL in patients with XLH, either children [13,14] or adults [15,16]. We therefore analyzed the HRQoL of patients with XLH in Spain in order to improve the care of patients with this rare disease.…”

X-Linked Hypophosphatemic Rickets: Multisystemic Disorder in Children Requiring Multidisciplinary Management

“…Few data are available on QoL and social impact for patients with XLH during childhood (5). A recent phase 3 trial study in children aged 5-12 years with XLH showed that switching from conventional treatment to burosumab therapy improved some measure of patient-reported outcomes as well as physical health score (82). Studies in adults with XLH showed a progressive reduction of QoL with the progression of the disease (22,47,83).…”

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium

“…Some patient-reported outcomes were significantly improved e.g. pain interference and physical health scores at week 40, although not for other outcomes or later time points (154). Some hypersensitivity and injection site reactions were noted in all trials, but there were no differences in serious treatment-related adverse events.…”