OBJECTIVES: XLH is a rare genetic disorder affecting the musculoskeletal system and is associated with significant clinical burden. The objective of this systematic review (SR) was to understand the humanistic and economic burden in patients with XLH.

METHODS: An SR was conducted using Embase^® and Medline^® databases, and conference proceedings. Studies published in English language reporting on the humanistic or economic burden of XLH in US and European populations were included.

RESULTS: Eleven publications reporting data from four unique studies met the eligibility criteria. Across the included studies, one study each reported data for France, UK and US, while one study reported combined data from 16 countries. Patients with XLH reported considerably worse quality of life (QoL) as evaluated using EQ-5D, VAS pain, SF36, and RAPID3 scales. In the EQ-5D assessment in adults, pain and discomfort posed most challenges, with 25% of patients reporting severe/extreme problems. Further, 21%, 16% and 13% of patients reported severe/extreme problems in mobility, self-care, and usual-activity domains, respectively. Most patients reported joint pain (89%), gait disturbance (86%) and bone pain (73%). A significantly lower QoL was observed in adults with XLH compared with adults with axial spondyloarthritis on VAS pain (p=0.008), SF36-PCS (p=0.029), and RAPID3 (p=0.017). Increased age, female gender, musculoskeletal fatigue and structural lesions such as osteoarthritis and enthesopathies, were significantly (p<0.05) associated with impaired QoL. In children, the major complications were bowing of the femur, tibia/fibula (87%), gait disturbance (86%), joint pain (64%), bone pain (59%) and restricted range of motion (41%). Considerable issues with pain, mobility and QoL were observed using PODCI and SF-10 scales compared to the general population. None of the included studies assessed the economic burden of XLH.

CONCLUSIONS: Limited available data suggest that patients with XLH have considerably impaired QoL. Quantification of economic burden of XLH is warranted.