Effectiveness of burosumab in children with X-linked hypophosphatemia with low rickets severity: SUNFLOWER analysis

Abstract Burosumab provides treatment benefits in children with X-linked hypophosphatemia. However, children with low rickets severity (Rickets Severity Score <2) were excluded from a previous phase 3, multicenter, active comparator-controlled randomized clinical trial. This descriptive interim analysis of the prospective SUNFLOWER cohort study included 69 children with X-linked hypophosphatemia aged ≤13 yr at enrollment. The burosumab and non-burosumab groups included 48 and 65 participants, respectively, with some overlap due to switching. Longitudinal changes in height and biochemical parameters (overall and stratified by disease severity [Rickets Severity Score <2/≥2; alkaline phosphatase </≥ upper limit of normal]) were assessed. In the burosumab all-patients analysis (irrespective of treatment duration or missing follow-up data), height Z-score (initiation: −2.04 ± 1.08; 3 yr: −1.58 ± 1.09), serum phosphate Z-score (initiation: −4.07 ± 1.77; 3 yr: −2.30 ± 1.45), 1,25(OH)2D (initiation: 39.79 ± 22.78 pg/mL; 3 yr: 84.35 ± 28.26 pg/mL), and ratio of tubular maximum phosphate reabsorption to glomerular filtration rate Z-score (initiation: −4.51 ± 2.60; 3 yr: −0.93 ± 2.50) tended to be higher at 3 yr following burosumab treatment. Rickets Severity Score (initiation: 2.38 ± 1.44; 3 yr: 0.83 ± 0.53) and alkaline phosphatase Z-score (initiation: 3.11 ± 1.79; 3 yr: 1.71 ± 1.14) tended to be lower at 3 yr. The subgroup analyses by Rickets Severity Score also showed similar results. Height Z-score, phosphate Z-score, and 1,25(OH)2D tended to be higher at 3 yr in both subgroups, while alkaline phosphatase Z-score tended to be lower. In the subgroup analysis by alkaline phosphatase status, height Z-score tended to be higher at 3 yr only in the ≥upper limit of normal subgroup; the other results were comparable. Overall, height, phosphate homeostasis, and bone health may improve in children with X-linked hypophosphatemia (including Rickets Severity Score <2) following burosumab treatment.