A Review of Dental Outcomes for Infants and Preschool Children Enrolled into a Clinical Trial of Asfotase Alfa for Early Onset Hypophosphatasia
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Introduction: Hypophosphatasia (HPP) is a highly variable genetic disease that impedes the development of teeth and bones. HPP is due to mutations in the ALPL gene which encodes the tissue non-specific form of alkaline phosphatase (TNSALP). Dental manifestations of HPP include painless premature exfoliation of primary teeth with intact roots. Until recently, there was no effective treatment for this disorder. Asfotase alfa is human recombinant bone-targeted ALP (StrensiqTM) (Alexion Pharmaceuticals, Inc. Boston, MA, USA). The purpose of this study was to review the development and exfoliation patterns of primary and permanent teeth in HPP patients with systemic HPP who were enrolled at the Canadian site in Winnipeg in a clinical trial of enzyme replacement therapy (ERT) with asfotase alfa. Methods: Data were collected from a cohort of hypophosphatasia patients ≤ 5 years of age at baseline who were enrolled at the Winnipeg site from locations across North America. Available dental data were recorded from a review of study files of enrolled patients at scheduled visits. In particular, exfoliation patterns and the eruption of deciduous and permanent teeth. Statistical analysis included descriptive and bivariate statistics (T tests and chi square analysis). A p value ≤ 0.05 was significant. Results: Eleven children (7 females, 4 males) with a mean age of 30 ± 27.1 months were enrolled at the Manitoba site in this 72-month clinical trial. Five were recruited in infancy (mean age 3.0 2.3 months) while the other 6 were recruited as preschool children (mean age 52.5 11.3months). Overall, children recruited as preschoolers had lost an average of 10.2 ± 3.9 of primary teeth prematurely due to HPP before enrollment. On average, children lost 2.3 2.9 number of teeth during this clinical trial. Participants recruited as infants prematurely lost significantly fewer teeth to early onset HPP during the trial period where started on ERT in infancy than those who were recruited as preschoolers and started on ERT at a later age (1.9 2.1 teeth vs. 10.2 3.9, p= 0.0043). Conclusion: Results suggest that there were fewer teeth prematurely lost because of HPP among children who began asfotase alfa treatment in infancy compared to those children recruited as preschoolers. This is the first demonstration, albeit on a small number of patients, that the oral health of children with confirmed systemic HPP with onset of signs and symptoms < 6 months of age might be improved with earlier and continued administration of ERT vs. later initiation of ERT.