Validation of the Radiographic Global Impression of Change (RGI-C) Score to Assess Healing of Rickets in Pediatric X-linked Hypophosphatemia (XLH).

Abstract Background Rickets is a primary manifestation of pediatric X-linked hypophosphatemia (XLH) – a rare progressive hereditary phosphate-wasting disease. Severity is quantified from radiographs using the Rickets Severity Scale (RSS). The Radiographic Global Impression of Change (RGI-C) is a complementary assessment in which a change score is assigned based on differences in the appearance of rickets on pairs of radiographs compared side by side. Objective The current study evaluated the reliability, validity, and sensitivity to change of the RGI-C specifically in pediatric XLH. Methods The reliability, validity, and sensitivity to change of the RGI-C were evaluated using data from two studies in pediatric XLH (113 children aged 1–12 years) in which burosumab treatment significantly improved rickets severity. Intra- and inter-rater reliability were assessed by three pediatric radiologists. Results Intra-rater reliability for RGI-C global score was >90% for agreement within 1 point, with weighted kappa values >0.5, indicating moderate to almost perfect agreement. Inter-rater reliability was also >90% (0.47–0.52 for all reader pairs; moderate agreement). The RGI-C global score showed significant relationships with changes from baseline to week 64 in serum phosphorus (r=−0.397), alkaline phosphatase (−0.611), total RSS (−0.672), standing height (0.268), and patient-reported global functioning (0.306) and comfort/pain functioning (0.409). Based on standardized response means, RGI-C global scores were sensitive to change in RSS, differentiating between those considered improved and greatly improved. Results for validity and sensitivity to change were similar for the RGI-C wrist, knee, and standing long leg scores. Conclusion The RGI-C is a reliable, valid, and sensitive measure in pediatric XLH, and complementary to the RSS.