OBJECTIVES: Excess FGF23 causes hypophosphatemia, leading to chronic debilitating musculoskeletal impairments in patients with X-linked hypophosphatemia (XLH). Treatments include burosumab, a fully-human monoclonal antibody to FGF23, or the combination of oral phosphate and active vitamin D (Pi/D). XLH symptoms in adults include bone/joint pain, stiffness, and fatigue. Previous research validated the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in adults with XLH. This study assesses burosumab impact on WOMAC among adults from an XLH Disease Monitoring Program (XLH-DMP; NCT03651505).

METHODS: The DMP is a 10-year study to collect real-world data on the safety and effectiveness of both Pi/D and burosumab for the treatment of XLH in adults and children. WOMAC has 24 items divided into three subscales: pain (5 items), stiffness (2 items), and physical function (PF, 17 items). WOMAC scores collected from adults at enrollment were compared to scores obtained one year later for three cohorts: 1, burosumab-naïve at enrollment with burosumab dosed within 90 days post-enrollment; 2, burosumab-naïve at enrollment with burosumab dosed between 91-180 days post-enrollment; 3, no-burosumab.

RESULTS: As of February 2022, 24 and 14 burosumab-naïve and 51 no-burosumab patients from North America were selected into cohort 1, 2 and 3. Average WOMAC scores were 35.6, 51.0, 32.8 for pain, stiffness, and PF for cohort 1, and 43.2, 51.8, 39.0 for cohort 2, and 24.8, 34.1, 19.3 for cohort 3 at enrollment. At year 1, reduction of 12.7, 13.5 and 9.4 scores were observed in pain, stiffness, and PF for cohort 1; and reduction of 16.1, 11.6, and 10.8 were observed for cohort 2. No-burosumab cohort had minimal changes.

CONCLUSIONS: Clinically meaningful improvement in pain (>9.7), stiffness (>10) and PF (>9.3) with burosumab were observed one year after enrollment among adults with XLH and were consistent with results from a randomized, double-blind placebo-controlled registration study.