Objectives: In X-linked hypophosphatemia (XLH), abnormally elevated serum Fibroblast growth Factor 23 (FGF23) results in low renal maximum threshold for phosphate reabsorption, low serum phosphorus, inappropriately normal 1,25-dihydroxyvitamin D, and development of rachitic deformities. The effect of KRN23 on health-related quality of life (HRQL) was assessed.
Methods: Open-label KRN23 was given s.c. every 28 days up to four doses to 28 adults with XLH (26 completers). KRN23 doses were given in a stepwise dose escalation algorithm: 0.05 to 0.10.3 to 0.6 mg/kg. HRQL (SF-36v2 and WOMAC) was measured at baseline and day 120. Eight SF-36v2 scales were evaluated: physical functioning (PF), role limitations due to physical health (RP), social functioning (SF), bodily pain (BP), general heath perceptions (GH), vitality (VT), role limitations due to emotional problems (RE), and mental health (MH). Physical component summary (PCS) and mental component summary (MCS) scores were derived. WOMAC scales included Pain, stiffness and physical functioning. Significance was declared for P<0.05.
Results: At baseline, mean BP, PF, RP, and PCS were far below those of the general USA population. At endpoint, mean MH and MCS became significantly higher than US norms; RP normalized; and PCS, BP, and PF remained below the norm. Scores for other domains remained comparable to the norm. Mean scores for all SF-36v2 domains increased and those for WOMAC decreased, indicating improvement in HRQL. Increases in RP, BP, and PCS (SF-36v2) and decreases in physical functioning and stiffness (WOMAC) were significant. At baseline, only GH, BP, and SF scores for XLH patients were significantly higher than a population with osteoarthritis; others were not significantly different. At endpoint, all mean SF-36v2 scores increased significantly relative to the osteoarthritis population for all except PF and RE.
Conclusions: Four monthly doses of KRN23 resulted in significantly improved patient HRQL.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology