Real-world effectiveness of burosumab in children with X-linked hypophosphatemic rickets

Paloian, Neil J.; Nemeth, Blaise A.; Sharafinski, Mark; Modaff, Peggy; Steiner, Robert D.

doi:10.1007/s00467-022-05484-7

Cited by 15 publications

(8 citation statements)

References 19 publications

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“…This prospective study is the first to report that the unique dental morphology of excessively larger pulp dimensions in patients with XLH persisted during three years of burosumab treatment. In line with previous reports, we also demonstrated that burosumab treatment normalized phosphate levels, contributing to the healing of rickets and to the improvement of linear growth of pediatric patients with XLH during the first year of treatment, with maintenance thereafter ( 25 , 26 ). Pediatric patients with XLH reportedly exhibited a delayed eruption of both deciduous and permanent teeth ( 27 ).…”

Section: Discussionsupporting

confidence: 92%

Dental health of pediatric patients with X-linked hypophosphatemia (XLH) after three years of burosumab therapy

et al. 2022

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An inactivating PHEX gene mutation with the resultant accumulation of several mineralization-inhibiting proteins (e.g., FGF23) causes skeletal and dental morbidity in X-linked hypophosphatemia (XLH). This prospective case-control study explored the effect of burosumab, an anti-FGF23 antibody, on dental health of children with XLH. Ten children (age 4.3-15 years) with XLH underwent burosumab treatment per protocol. Assessment of their dental status at treatment initiation and after 1 and 3 years of treatment included clinical, laboratory and radiographic evaluation of rickets and dentition. Orthopantomographic examinations of ten healthy sex- and age-matched controls were selected for comparison. Coronal and pulp dimensions of a selected permanent mandibular molar were measured with Planmeca Romexis® software. One year of treatment led to improvement of height z-score (p=0.019) and healing of the rickets (p<0.001) in the XLH patients, and those achievements were maintained after three years of treatment. Dental morphology of XLH patients, distinguished by increased pulp-coronal ratios compared to controls (p=0.002), remained larger after the first year of treatment (p<0.001) and did not attain the decrease expected with age after three years of treatment. Five patients had a history of recurrent dental abscesses, with three having undergone at least one episode during the year before burosumab initiation. One patient sustained recurrent abscesses throughout three years of treatment. The persistence of the unique dental morphology of XLH patients undergoing burosumab therapy, as evidenced by excessively larger pulp dimensions, supports the role of other PHEX gene-related local mineralization inhibitors, such as osteopontin, in the pathogenesis of dental morbidity.

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Section: Discussionsupporting

confidence: 92%

Dental health of pediatric patients with X-linked hypophosphatemia (XLH) after three years of burosumab therapy

et al. 2022

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“…Burosumab represents a novel therapeutic strategy for managing XLH, by addressing the underlying pathophysiology of the disorder [25]. Our study demonstrated that transition from conventional therapy to burosumab injections signi cantly improved phosphorus homeostasis, thus corroborating results of previous trials [15,[26][27][28]. Phosphorus levels improved relatively quickly.…”

Section: Discussionsupporting

confidence: 86%

Linear growth of children with X-linked hypophosphatemia treated with burosumab: a real-life observational study

Levy-Shraga,

Levi,

Regev

et al. 2023

Eur J Pediatr

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To assess the long-term e cacy of burosumab for paediatric patients with X-linked hypophosphatemia, focusing on linear growth. MethodsThis multi-center retrospective study included 35 paediatric patients who began treatment with burosumab between January 2018 and January 2021. We collected clinical data, anthropometric measurements, laboratory results and rickets severity score (RSS), from two years prior to treatment initiation and up to four years after. ResultsBurosumab was initiated at a mean age of 7.5 ± 4.4 years (range 0.6-15.9), with a mean initial dose of 0.8 ± 0.3 mg/kg, which was subsequently increased to 1.1 ± 0.4 mg/kg. The patients were followed for 2.9 ± 1.4 years (range 1-4) after initiating burosumab. Serum phosphorus levels increased from 2.7 ± 0.8 mg/dl at burosumab initiation to 3.4 ± 0.6 mg/dl after three months, and remained stable (p < 0.001). Total reabsorption of phosphorus increased from 82.0 ± 6.8% to 90.1 ± 5.3% after 12 months of treatment (p = 0.041). The RSS improved from 1.7 ± 1.0 at burosumab initiation to 0.5 ± 0.6 and 0.3 ± 0.6 after 12 and 24 months, respectively (p < 0.001). Both height z-score and weight z-score improved from burosumab initiation to the end of the study: from − 2.07 ± 1.05 to -1.72 ± 1.04 (p < 0.001), and from − 0.51 ± 1.12 to -0.11 ± 1.29 (p < 0.001), respectively. Eight children received growth hormone combined with burosumab treatment. Height z-score improved among those who received growth hormone (from − 2.33 ± 1.12 to -1.94 ± 1.24, p = 0.042) and among those who did not (from − 2.01 ± 1.01 to -1.66 ± 1.01, p = 0.001). ConclusionBurosumab treatment in a real-life setting improved phosphate homeostasis and rickets severity, and enhanced linear growth. What is knownBurosumab was approved in 2018 as a standalone treatment for XLH.Compared to conventional therapy, burosumab treatment has been shown to increase serum phosphate levels and reduce the severity of rickets.The effect of burosumab on growth is still being study. What is new:Height z-score improved between the start of burosumab treatment and the end of the study (-2.07±1.05 vs. -1.72±1.04, p < 0.001).Eight children received burosumab combined with growth hormone treatment without side effects during the concomitant treatments. Height z-score improved among those who received growth hormone (from -2.33±1.12 to -1.94±1.24, p=0.042) and among those who did not (from -2.01±1.01 to -1.66±1.01, p=0.001).

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“…In a study of 61 children with XLH ( 20 ), aged 1–12 years, burosumab treatment for 64 weeks was associated with improvements in phosphate metabolism compared to conventional treatment, as well as with reductions in total RSS by -0.9 in younger children under 5 years old (n=26) and by -1.4 in children aged 5–12 years (n=35). Transition from conventional therapy to burosumab therapy in 12 children and adolescents aged 1–18 years with XLH ( 21 ) was associated with an increase in mean serum phosphate from 2.6 mg/dL to 3.4 mg/dL 4 weeks after starting burosumab (p=0.004), which was sustained at 12 months post-burosumab (mean serum phosphate 3.5 mg/dL; p<0.001). Average RSS derived from lower-extremity radiographs were reduced from 3.0 prior to transition from burosumab to 1.4 after 24 months following transition (p<0.001).…”

Section: Introductionmentioning

confidence: 99%

Burosumab for X-linked hypophosphatemia in children and adolescents: Opinion based on early experience in seven European countries

Mughal

Baroncelli²,

Lucas-Collantes

et al. 2023

Front. Endocrinol.

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Given the relatively recent introduction of burosumab in the management of X-linked hypophosphatemia (XLH), there is limited real-world data to guide its use in clinical practice. As a group of European physicians experienced with burosumab treatment in clinical practice, we convened with the objective of sharing these practice-based insights on the use of burosumab in children and adolescents with XLH. We attended two virtual meetings, then discussed key questions via Within3, a virtual online platform. Points of discussion related to patient selection criteria, burosumab starting dose, dose titration and treatment monitoring. Our discussions revealed that criteria for selecting children with XLH varied across Europe from all children above 1 year to only children with overt rickets despite conventional treatment being eligible. We initiated burosumab dosing according to guidance in the Summary of Product Characteristics, an international consensus statement from 2019 and local country guidelines. Dose titration was primarily guided by serum phosphate levels, with some centers also using the ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate (TmP/GFR). We monitored response to burosumab treatment clinically (growth, deformities, bone pain and physical functioning), radiologically (rickets and deformities) and biochemically (serum phosphate, alkaline phosphatase, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, urine calcium-creatinine ratio and TmP/GFR). Key suggestions made by our group were initiation of burosumab treatment in children as early as possible, from the age of 1 year, particularly in those with profound rickets, and a need for clinical studies on continuation of burosumab throughout adolescence and into adulthood.

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Real-world effectiveness of burosumab in children with X-linked hypophosphatemic rickets

Cited by 15 publications

References 19 publications

Dental health of pediatric patients with X-linked hypophosphatemia (XLH) after three years of burosumab therapy

Dental health of pediatric patients with X-linked hypophosphatemia (XLH) after three years of burosumab therapy

Linear growth of children with X-linked hypophosphatemia treated with burosumab: a real-life observational study

Burosumab for X-linked hypophosphatemia in children and adolescents: Opinion based on early experience in seven European countries

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