Real-World Effectiveness of Burosumab Versus Oral Phosphate and Active Vitamin D in Adults With X-Linked Hypophosphatemia.

In X-linked hypophosphatemia (XLH), PHEX gene variants lead to elevated FGF23 production, resulting in hypophosphatemia, osteomalacia, osteomalacia-related fractures, osteoarthritis, enthesopathy, spinal stenosis, and symptoms of pain, stiffness, and decreased physical function. Burosumab is an anti-FGF23 monoclonal antibody approved for XLH treatment. Randomized studies comparing oral phosphate/active vitamin D (Pi/D) to burosumab in adults are lacking. This analysis, which utilized real-world data from the prospective, Americas-based XLH Disease Monitoring Program (NCT03651505), evaluated the effectiveness of burosumab versus Pi/D, based on changes from baseline to the year 1 visit in serum phosphate, 1,25-dihydroxyvitamin D (1,25[OH]2D), parathyroid hormone (PTH), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS PF), and Timed Up and Go (TUG) performance outcome. 2 cohorts of adults with XLH who either began burosumab between baseline and the year 1 visit (n = 65) or were on Pi/D (n = 74) at study entry and did not receive burosumab were included. Inverse probability of treatment weighting was employed to adjust for potential confounding due to baseline cohort differences. At the year 1 visit, mean (standard error) change from baseline was significant for burosumab versus Pi/D in serum phosphate (0.78 [0.08] vs 0.15 [0.14] mg/dL; p < .001), 1,25(OH)2D (19.41 [3.39] vs 5.49 [3.43] pg/mL; p = .011), PTH (-13.82 [5.00] vs 11.79 [8.10] pg/mL; p = .006), WOMAC pain (-7.50 [2.34] vs 4.47 [3.23]; p = .004), WOMAC physical function (-5.68 [1.96] vs 6.77 [4.85]; p = .006), and WOMAC total (-7.78 [2.06] vs 3.15 [3.37]; p = .005) scores, PROMIS PF (1.51 [0.73] vs -1.64 [1.11], p = .018), and TUG (-1.19 [0.42] vs 0.55 [0.43] seconds, p = .011). A trend towards improved WOMAC stiffness was observed for burosumab (-10.16 [2.85] vs -1.79 [3.68]; p = .086). In this real-world analysis of adults with XLH, burosumab treatment was associated with improved biochemical parameters, pain, physical function, and mobility compared with Pi/D.