Real-World Effectiveness of Burosumab Versus Oral Phosphate and Active Vitamin D in Adults with X-Linked Hypophosphatemia (XLH): A 3-Year Follow-Up of the XLH Disease Monitoring Program.

X-linked hypophosphatemia (XLH) is a progressive disease in which excess FGF23 causes renal phosphate wasting, leading to hypophosphatemia. Consequences in adults include osteomalacia, fractures, pseudofractures, joint dysfunction, pain, and impaired mobility. Treatments for XLH are the anti-FGF23 antibody burosumab and active forms of vitamin D alone or in combination with oral phosphate (Pi/D). Randomized studies comparing burosumab with Pi/D in adults with XLH are lacking. We present a 3-yr follow-up analysis evaluating real-world effectiveness of burosumab versus Pi/D based on biochemistry and standardized symptom assessments (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) using data from the XLH Disease Monitoring Program (DMP; NCT03651505), a prospective, Americas-based study. Adults with XLH initiated burosumab between baseline and the year 1 visit (N = 54) or reported being on Pi/D therapy at enrollment (N = 55) were included. After adjusting for baseline differences using inverse probability of treatment weighting, the data showed a significantly higher mean (SD) change from baseline in serum phosphate with burosumab versus Pi/D (year 1: 0.8 [0.8] vs 0.1 [0.7] mg/dL; year 3: 0.6 [0.8] vs 0.1 [0.7] mg/dL, both p < .001). A higher proportion of burosumab versus Pi/D participants achieved serum phosphate levels above the lower limit of normal (2.5 mg/dL; year 1: 70.5% vs 18.8%; year 3: 60.8% vs 25.0%, both p < .001). At year 1, changes from baseline in WOMAC pain (-6.3 [27.7] vs 2.1 [22.4], p = .055), physical function (-6.4 [19.1] vs 0.1 [29.0], p = .122), and stiffness (-11.1 [32.1] vs -2.3 [33.7], p = .073) were not statistically significant between cohorts, but were significant at year 3 (pain: -9.8 [22.6] vs 3.3 [24.1], p < .001; physical function: -10.0 [25.7] vs 3.3 [24.7], p = .001; stiffness: -15.2 [29.5] vs -3.7 [31.4], p = .016). In this real-world analysis of adults with XLH over a 3-yr follow-up, burosumab treatment was associated with improved serum phosphate and patient-reported outcomes versus Pi/D.