Clinical profiles of treated and untreated adults with hypophosphatasia in the Global HPP Registry

Abstract

Background: The clinical signs and symptoms of hypophosphatasia (HPP) can manifest during any stage of life. The age at which a patient's symptoms are reported can impact access to targeted treatment with enzyme replacement therapy (asfotase alfa), as this treatment is indicated for patients with pediatric-onset HPP in most countries. As such, many patients reported to have adult-onset HPP typically do not receive treatment. Comparison of the disease in treated and untreated adult patients is confounded by the approved indication. To avoid this confounding factor, a comparison between baseline disease manifestations prominent among treated versus untreated adult patients was limited to those with pediatric-onset HPP using data collected from the Global HPP Registry. The hypothesis was that treated adults will have a greater disease burden at baseline than untreated adults. The analysis of disease manifestations in adults with adult-onset HPP was conducted separately.

Results: A total of 398 adults with HPP were included; 213 with pediatric-onset (114 treated, 99 untreated) and 141 with adult-onset HPP (2 treated and 139 untreated). The treated, pediatric-onset patients were more likely to have a history of pain (prevalence ratio [PR]: 1.3, 95% confidence interval [CI] 1.1, 1.4), skeletal (PR: 1.3, 95% CI 1.1, 1.6), constitutional/metabolic (PR: 1.7, 95% CI 1.3, 2.0), muscular (PR: 1.8, 95% CI 1.4, 2.1) and neurological (PR: 1.7, 95% CI 1.1, 2.3) manifestations of HPP, and also had poorer measures for health-related quality of life, pain, and disability compared with untreated pediatric-onset patients. In patients with adult-onset HPP, the most frequent signs and symptoms were chronic bone pain (52.5%), dental manifestations (42.6%), fatigue (23.4%), recurrent fractures or pseudofractures (22.0%), and generalized body pain (22.0%).

Conclusions: Along with the more classical skeletal signs and symptoms, pain, muscular, and constitutional/metabolic manifestations are common in adults with HPP, regardless of age of disease onset, highlighting a full spectrum of HPP manifestations.

Keywords: Burden of disease; Enzyme replacement therapy; HRQoL; Hypophosphatasia.

Fig. 1

History of HPP manifestations at baseline among treated (n = 99) and untreated (n = 114) adults with pediatric-onset HPP. ^aPR of treated adults/untreated adults with pediatric-onset HPP. PR > 1 represents an increased likelihood that treated patients had a history of the indicated HPP manifestation. Numbers in bold represent PRs with 95% CI values > 1. ^bIncludes loss of permanent teeth, loose teeth, poor dentition, hypodontia, dental implants, dental bridges, and dentures. CI, confidence interval; HPP, hypophosphatasia; PR, prevalence ratio

Fig. 2

Summary of mean SF-36v2 scores at baseline among treated and untreated adults with pediatric-onset HPP. ^aBefore the start of ERT. ^bBased on normative data reported in Ware et al.³ for the 1998 US general population. ERT, enzyme replacement therapy; HPP, hypophosphatasia; HRQoL, health-related quality of life; SD, standard deviation; SF-36v2, 36-item Short Form Health Survey version 2; US, United States

Fig. 3

Pain and disability at baseline among adults with pediatric-onset HPP: overall and by treatment status. ^aComparison between untreated and treated. ^bBefore the start of ERT. BPI-SF, Brief Pain Inventory Short Form; ERT, enzyme replacement therapy; HAQ-DI, Health Assessment Questionnaire Disability Index; HPP, hypophosphatasia

Fig. 4

History of HPP manifestations at baseline among adults with adult-onset HPP (n = 141). ^aIncludes loss of permanent teeth, loose teeth, poor dentition, hypodontia, dental implants, dental bridges, and dentures. HPP, hypophosphatasia