FGF23 measurement in burosumab-treated patients: an emerging treatment may induce a new analytical interference

Piketty, Marie-Liesse; Souberbielle, Jean‐Claude; Maruani, Gérard; Audrain, Christelle; Rothenbühler, Anya; Prié, Dominique; Linglart, Agnès

doi:10.1515/cclm-2020-0460

Cited by 18 publications

(14 citation statements)

References 8 publications

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“…In treated patients with an unclear diagnosis, it is recommended to stop phosphate supplements (for at least two weeks) before measuring FGF23, because phosphate supplements may increase FGF23. Burosumab therapy (see Burosumab below) may cause analytical interference with certain FGF23 assays ( 95 ), but FGF23 measurements are not recommended during the follow-up of XLH patients (see Burosumab below). Thus, standardization and harmonization of FGF23 assays remain lacking, and results should always be interpreted cautiously.…”

Section: Resultsmentioning

confidence: 99%

“…In patients receiving active vitamin D analogs and phosphate however, monitoring of 1,25(OH) 2 D is not recommended, because supraphysiological doses may be required to maintain PTH and calciuria within the desired range. Measuring FGF23 is not useful during follow-up of XLH patients, especially in patients treated with burosumab which may cause analytical interference ( 95 ).…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidisciplinary group of Belgian experts convened to discuss translation of international best available evidence into locally feasible consensus recommendations. Patients with XLH may present to a wide array of primary, secondary and tertiary care physicians, among whom awareness of the disease should be raised. XLH has a very broad differential-diagnosis for which clinical features, biochemical and genetic testing in centers of expertise are recommended. Optimal care requires a multidisciplinary approach, guided by an expert in metabolic bone diseases and involving (according to the individual patient’s needs) pediatric and adult medical specialties and paramedical caregivers, including but not limited to general practitioners, dentists, radiologists and orthopedic surgeons. In children with severe or refractory symptoms, FGF23 inhibition using burosumab may provide superior outcomes compared to conventional medical therapy with phosphate supplements and active vitamin D analogues. Burosumab has also demonstrated promising results in adults on certain clinical outcomes such as pseudofractures. In summary, this work outlines recommendations for clinicians and policymakers, with a vision for improving the diagnostic and therapeutic landscape for XLH patients in Belgium.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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“…Burosumab is a fully human IgG1 mAb that binds intact FGF23. In vitro, burosumab inhibits recognition of the intact FGF23 molecule by preventing binding of one or both reagent Abs in sandwich two-site assays, indicating that the intact FGF23 molecules were no longer recognized in vitro [79].…”

Section: Fibroblast Growth Factor 23 (Fgf23)mentioning

confidence: 99%

Hormone Immunoassay Interference: A 2021 Update

et al. 2022

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Immunoassays are powerful qualitative and quantitative analytical techniques. Since the first description of an immunoassay method in 1959, advances have been made in assay designs and analytical characteristics, opening the door for their widespread implementation in clinical laboratories. Clinical endocrinology is closely linked to laboratory medicine because hormone quantification is important for the diagnosis, treatment, and prognosis of endocrine disorders. Several interferences in immunoassays have been identified through the years; although some are no longer encountered in daily practice, cross-reaction, heterophile antibodies, biotin, and anti-analyte antibodies still cause problems. Newer interferences are also emerging with the development of new therapies. The interfering substance may be exogenous (e.g., a drug or substance absorbed by the patient) or endogenous (e.g., antibodies produced by the patient), and the bias caused by interference can be positive or negative. The consequences of interference can be deleterious when clinicians consider erroneous results to establish a diagnosis, leading to unnecessary explorations or inappropriate treatments. Clinical laboratories and manufacturers continue to investigate methods for the detection, elimination, and prevention of interferences. However, no system is completely devoid of such incidents. In this review, we focus on the analytical interferences encountered in daily practice and possible solutions for their detection or elimination.

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“…In addition, monitoring of renal phosphorus threshold concentration (TmP/GFR) is recommended in these patients, in order to confirm improvement of renal phosphate wasting [ 9 ]. Monitoring of FGF23 serum levels is not recommended in patients on burosumab treatment, as current assays cannot discriminate between burosumab-bound and free FGF23, resulting in unreliable results [ 21 ]. Normalization of initially low urinary calcium excretion, which is especially the case in children with calcipenic rickets, approves adequate calcium intake.…”

Section: General Approachmentioning

confidence: 99%

Rickets guidance: part II—management

et al. 2022

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Here, we discuss the management of different forms of rickets, including new therapeutic approaches based on recent guidelines. Management includes close monitoring of growth, the degree of leg bowing, bone pain, serum phosphate, calcium, alkaline phosphatase as a surrogate marker of osteoblast activity and thus degree of rickets, parathyroid hormone, 25-hydroxyvitamin D3, and calciuria. An adequate calcium intake and normal 25-hydroxyvitamin D3 levels should be assured in all patients. Children with calcipenic rickets require the supplementation or pharmacological treatment with native or active vitamin D depending on the underlying pathophysiology. Treatment of phosphopenic rickets depends on the underlying pathophysiology. Fibroblast-growth factor 23 (FGF23)-associated hypophosphatemic rickets was historically treated with frequent doses of oral phosphate salts in combination with active vitamin D, whereas tumor-induced osteomalacia (TIO) should primarily undergo tumor resection, if possible. Burosumab, a fully humanized FGF23-antibody, was recently approved for treatment of X-linked hypophosphatemia (XLH) and TIO and shown to be superior for treatment of XLH compared to conventional treatment. Forms of hypophosphatemic rickets independent of FGF23 due to genetic defects of renal tubular phosphate reabsorption are treated with oral phosphate only, since they are associated with excessive 1,25-dihydroxyvitamin D production. Finally, forms of hypophosphatemic rickets caused by Fanconi syndrome, such as nephropathic cystinosis and Dent disease require disease-specific treatment in addition to phosphate supplements and active vitamin D. Adjustment of medication should be done with consideration of treatment-associated side effects, including diarrhea, gastrointestinal discomfort, hypercalciuria, secondary hyperparathyroidism, and development of nephrocalcinosis or nephrolithiasis.

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FGF23 measurement in burosumab-treated patients: an emerging treatment may induce a new analytical interference

Cited by 18 publications

References 8 publications

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

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

Hormone Immunoassay Interference: A 2021 Update

Rickets guidance: part II—management

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