Gathering 10 years of real-world FGF23-related hypophosphatemic rickets and osteomalacia data in GCC countries through a non-interventional registry: study protocol.

Background Hypophosphatemic rickets (HR) and osteomalacia related to fibroblast growth factor 23 (FGF23) are rare, lifelong disorders characterized by phosphate wasting, resulting in defective bone mineralization, multisystem manifestations, and reduced quality of life (QoL). Excess FGF23 is central to the pathophysiology of many HR subtypes, including X-linked hypophosphatemia (XLH). Supplementation with oral phosphate and active vitamin D analogs is often ineffective and associated with side effects. Burosumab, a fully humanized monoclonal immunoglobulin G1 antibody that inhibits FGF23, has been approved in the Gulf Cooperation Council (GCC) countries for the treatment of XLH and tumor-induced osteomalacia. Epidemiological, treatment, resource utilization, and outcomes data on FGF23-related HR and osteomalacia are limited in the Middle East region. Methods We present a 10-year, multicenter, non-interventional registry of patients with FGF23-related HR/osteomalacia at 14 sites across the Gulf Cooperation Council (GCC) countries. Up to 200 patients of any age or sex with a confirmed diagnosis of FGF23-related HR/osteomalacia have been enrolled over five years (June 2020 to June 2025), with follow-up extending five years post-enrollment. Retrospective data include a three-year look-back period from the date of diagnosis; prospective data will be collected biannually during routine clinical visits. The study will generate up to ten years of real-world data, with the last patient follow-up concluding in 2030. The primary study objective is to characterize the burden, progression, treatment patterns, and long-term outcomes of FGF23-related HR/osteomalacia. Secondary objectives include evaluations of treatment effectiveness, safety, and QoL, using patient-reported outcome tools – the Short Form-36 (SF-36) for adults and the Pediatric Quality of Life Inventory (PedsQL) for children <18 years – completed approximately every six months during routine visits. Exploratory analyses will focus on healthcare resource utilization. All reporting will be consistent with the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) Initiative checklist for cohort studies. Conclusions This 10-year regional rare disease registry aims to fill critical knowledge gaps regarding epidemiology, real-world treatment, and outcomes of FGF23-related HR and osteomalacia in the GCC. Insights will seek to inform clinical decision-making, optimize management strategies, and improve patient outcomes. Findings will also contribute to the global understanding of FGF23-related disorders.