Switching from conventional therapy to Crysvita (burosumab) leads to clinically relevant reductions in pain and fatigue, and better quality of life, in children with X-linked hypophosphatemia (XLH) ages 5 to 12, according to data from a Phase 3 clinical trial.
These findings in patient-reported outcomes add to previous results from this trial showing that the therapy significantly lessened the severity of bone-related symptoms and aided growth in pediatric patients, ages 1 to 12.
Altogether, these data support Crysvita’s benefits in children with XLH.
The results were described in the study “Patient-Reported Outcomes from a Randomized, Active-Controlled, Open-Label, Phase 3 Trial of Burosumab Versus Conventional Therapy in Children with X-Linked Hypophosphatemia,” published in the journal Calcified Tissue International.
Crysvita, marketed by Ultragenyx Pharmaceutical and Kyowa Kirin, is currently the only disease-modifying therapy approved for XLH. It works by blocking FGF23, a bone-derived hormone that is overly produced in XLH patients.
Abnormally high blood levels of FGF23 result in the excessive loss of phosphate via urine, and lower-than-normal blood levels of this important bone component.
As such, the therapy is thought to boost phosphate reabsorption in the kidneys and increase its levels in the blood, ultimately easing rickets and other XLH symptoms.
An international Phase 3 clinical trial (NCT02915705) evaluated the safety and effectiveness of Crysvita against conventional therapy — phosphate and vitamin D supplements — in 61 children with XLH, ages 1 to 12. Participants were randomly assigned to either an under-the-skin injection of Crysvita every two weeks, or to continue with standard therapy for 64 weeks (more than one year).
Previously published results showed that Crysvita was superior to conventional treatment at all key goals, including significantly lessening the severity of rickets and lower limb deformity, as well as improving growth and physical function.
As secondary and exploratory goals, the researchers also evaluated patients’ views of changes with treatment using the Patient-Reported Outcomes Measurement Information System (PROMIS), the Short Form-10 Health Survey for Children — which assesses health-related quality of life — and the Faces Pain Scale–Revised.
Funded by the National Institutes of Health, PROMIS provides a set of patient-reported measures to assess a disease’s impact on physical, mental, and social well-being. The selected PROMIS questionnaires evaluated pain interference with a patient’s life, physical function, and fatigue.
All children ages 5 and older at enrollment (15 assigned to Crysvita and 20 to standard treatment), or their caregivers, completed these questionnaires at the beginning of the study, and at weeks 24, 40, and 64.
As the trial was not designed to assess group differences for secondary and exploratory goals, three-point changes in patient-reported outcomes within groups were considered clinically relevant, based on previous studies.
These newly published data cover 35 children (mean age of 8.5), and show that Crysvita resulted in clinically relevant reductions in pain interference and in fatigue by week 40, which were maintained at week 64. In addition, Crysvita-treated children showed greater improvements in physical function than those on standard treatment, but these did not reach the clinically relevant threshold.
No clinically relevant changes in these outcomes were observed among those on conventional therapy over this same time.
Group differences only reached statistical significance for pain interference up to week 40. The lack of a persistent effect up to week 64 may be explained by the small number of patients and the fact that Crysvita’s benefits “may not be sufficient to fully address all aspects of pain syndrome over a short period of time,” the researchers wrote.
Crysvita also significantly improved the quality-of-life physical health domain in these children by about 10% at weeks 40 and 64. At all study visits, the children reported no pain, suggesting that the selected pain scale “may not reliably assess the burden of pain severity in this population,” they added.
Overall, these findings highlighted that changing from conventional therapy to Crysvita was associated with slight improvements in mobility, clinically meaningful drops in pain interference and fatigue, and statistically significant improvements in the physical health of children ages 5–12 years with XLH.
“Further follow-up is warranted to determine longer-term effects on [health-related quality of life] and patient-reported pain interference, physical function mobility, and fatigue,” the researchers wrote.
They suggested that the general absence of statistically significant differences between groups may also be related to higher compliance and adherence to conventional treatment in clinical trial settings, which can result in greater health improvements than are seen in routine standard care.
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