Health-Related Quality of Life (HRQoL) Impacts in Individuals With Hypophosphatasia (HPP): A Systematic Literature Review (SLR)
Author(s)
Eric T. Rush, MD1, Suzanne McMullen, MHA2, Fernanda Nagase, MSc2, Antoinette Cheung, MPH2, Benit Maru, PhD3, Kathryn M. Dahir, MD4.
1Children's Mercy Hospital, Kansas City, KS, USA, 2Broadstreet HEOR, Vancouver, BC, Canada, 3Alesta Therapeutics BV, Leiden, Netherlands, 4Vanderbilt University Medical Center, Nashville, TN, USA.
1Children's Mercy Hospital, Kansas City, KS, USA, 2Broadstreet HEOR, Vancouver, BC, Canada, 3Alesta Therapeutics BV, Leiden, Netherlands, 4Vanderbilt University Medical Center, Nashville, TN, USA.
OBJECTIVES: HPP is a multisystem disorder affecting bone, teeth and other organs, all of which impact HRQoL. With limited treatment options, adults with HPP face considerable unmet needs.
METHODS: An SLR of MEDLINE, Embase, and Northern Lights was conducted to characterize HRQoL in adults with HPP. Outcomes were summarized by narrative synthesis.
RESULTS: In total, 21 publications (n=15-685 patients) assessed HRQoL in adults with HPP; instruments included: 36- and 12-Item Short-form Survey (SF-36/-12; n=14 publications), Brief Pain Inventory (BPI; n=8), Health Assessment Questionnaire Disability Index (HAQ-DI; n=7), Fatigue Severity Scale (FSS; n=4), and Work Productivity and Activity Impairment (WPAI; n=2). Six publications described HRQoL burden of adults in the Global HPP Registry. SF-36 scores were below population norms across physical domains, regardless of skeletal or muscular/pain manifestations. One analysis found worse BPI scores with more HPP manifestations. Adults with HPP had higher levels of disability (worse HAQ-DI scores) than population norms. A single-center cross-sectional study reported higher fatigue levels in adults with HPP versus healthy individuals (FSS: 3.7 vs 2.7, respectively), though mental well-being was comparable. Four cohort studies and one trial assessed treatment effects. In two cohort studies, SF-36 Physical Component Summary (PCS) scores improved significantly with enzyme replacement therapy; in one study, work productivity improved within one year of treatment, though gains reversed or plateaued thereafter. Evidence on pain following treatment was inconsistent, and no significant improvements were reported in mental well-being (two studies), or disability scores (one study).
CONCLUSIONS: Evidence suggests adults with HPP experience substantial impacts in physical functioning, fatigue, and disability although findings vary by study design and size. Lack of validated instruments for HPP may also impact findings. Though available therapies provided benefits, improvements in components of HRQoL, including pain, mental well-being and disability, were unclear. These findings highlight the need for new interventions that deliver sustained improvements.
METHODS: An SLR of MEDLINE, Embase, and Northern Lights was conducted to characterize HRQoL in adults with HPP. Outcomes were summarized by narrative synthesis.
RESULTS: In total, 21 publications (n=15-685 patients) assessed HRQoL in adults with HPP; instruments included: 36- and 12-Item Short-form Survey (SF-36/-12; n=14 publications), Brief Pain Inventory (BPI; n=8), Health Assessment Questionnaire Disability Index (HAQ-DI; n=7), Fatigue Severity Scale (FSS; n=4), and Work Productivity and Activity Impairment (WPAI; n=2). Six publications described HRQoL burden of adults in the Global HPP Registry. SF-36 scores were below population norms across physical domains, regardless of skeletal or muscular/pain manifestations. One analysis found worse BPI scores with more HPP manifestations. Adults with HPP had higher levels of disability (worse HAQ-DI scores) than population norms. A single-center cross-sectional study reported higher fatigue levels in adults with HPP versus healthy individuals (FSS: 3.7 vs 2.7, respectively), though mental well-being was comparable. Four cohort studies and one trial assessed treatment effects. In two cohort studies, SF-36 Physical Component Summary (PCS) scores improved significantly with enzyme replacement therapy; in one study, work productivity improved within one year of treatment, though gains reversed or plateaued thereafter. Evidence on pain following treatment was inconsistent, and no significant improvements were reported in mental well-being (two studies), or disability scores (one study).
CONCLUSIONS: Evidence suggests adults with HPP experience substantial impacts in physical functioning, fatigue, and disability although findings vary by study design and size. Lack of validated instruments for HPP may also impact findings. Though available therapies provided benefits, improvements in components of HRQoL, including pain, mental well-being and disability, were unclear. These findings highlight the need for new interventions that deliver sustained improvements.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO130
Topic
Clinical Outcomes, Patient-Centered Research, Study Approaches
Topic Subcategory
Clinical Outcomes Assessment
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Rare & Orphan Diseases