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

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Abstract

Background

X-linked hypophosphatemic rickets (XLH) is the most common cause of inherited rickets. Historically, XLH was treated with oral phosphate and calcitriol (conventional treatment). Burosumab, a fibroblast growth factor 23 (FGF-23) monoclonal antibody, was approved by the United States Food and Drug Administration (FDA) in 2018 for XLH treatment. Nevertheless, conventional treatment of XLH continues to be recommended by some specialists due to lack of published experience with burosumab in the clinical setting. We compared laboratory and radiographic changes observed following transition from conventional therapy to burosumab in pediatric XLH patients as part of routine care.

Methods

This retrospective single-center study identified and retroactively studied twelve patients aged 1–18 years old with XLH previously treated with conventional therapy and transitioned to burosumab. Laboratory studies and radiographs were obtained routinely as standard of care during two treatment periods: (1) conventional therapy and (2) burosumab treatment. Laboratory values and radiologic rickets severity scores were compared between periods.

Results

All laboratory values demonstrated improvement following 1 month of burosumab treatment, findings which were sustained over the 2-year study period. Rickets severity scores and height z-scores also improved with burosumab. There were no serious adverse events with burosumab, and adverse events overall were very infrequent and mild. One patient developed an asymptomatic mild elevation of serum phosphate while taking burosumab resulting in a temporary pause in therapy.

Conclusions

Safety and effectiveness of burosumab in treatment of XLH were demonstrated as burosumab yielded statistically significant improvement in laboratory and radiographic markers of rickets and height compared to conventional therapy.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information.

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Data availability

Dataset generated from retrospective medical chart review and is available upon request.

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Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI, 53792, USA

    Neil J. Paloian, Peggy Modaff & Robert D. Steiner

  2. Department of Orthopedics and Rehabilitation, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Blaise Nemeth

  3. Department of Radiology, Aurora Healthcare, Milwaukee, WI, USA

    Mark Sharafinski

Authors
  1. Neil J. Paloian
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  2. Blaise Nemeth
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  3. Mark Sharafinski
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  4. Peggy Modaff
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  5. Robert D. Steiner
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Contributions

Dr. Paloian conceptualized and designed the study, coordinated and supervised data collection, performed the data analysis, drafted the initial manuscript, and reviewed and revised the manuscript. Drs. Nemeth and Sharafinski performed the radiographic interpretations and reviewed and revised the manuscript. Ms. Modaff and Dr. Steiner conceptualized and designed the study and reviewed and revised the manuscript, revising it critically for important intellectual content.

Corresponding author

Correspondence to Neil J. Paloian.

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Ethics approval

Study approved by the University of Wisconsin-Madison Health Sciences Institutional Review Board.

Consent to participate

Waiver of informed consent granted by IRB.

Consent for publication

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Conflict of interest

Neil Paloian is a member of the speaker’s bureau of Ultragenyx pharmaceuticals. Robert D. Steiner reports equity interest in and consulting fees from Acer Therapeutics and PTC Therapeutics. He also reports leading an investigator-initiated observational research study funded by Alexion via contract with Marshfield Clinic Health System, and consulting fees from Alexion, Best Doctors, E-Scape Bio, Health Advances, Precision for Value, and Travere, and honoraria from Medscape/WebMD and The France Foundation as well as employment with Prevention Genetics. The other authors have no relevant conflicts of interest or financial or proprietary interests to disclose.

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Cite this article

Paloian, N.J., Nemeth, B., Sharafinski, M. et al. Real-world effectiveness of burosumab in children with X-linked hypophosphatemic rickets. Pediatr Nephrol 37, 2667–2677 (2022). https://doi.org/10.1007/s00467-022-05484-7

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  • DOI: https://doi.org/10.1007/s00467-022-05484-7

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