Bone Abstracts

Objectives: X-linked hypophosphataemia (XLH) is a rare, inherited, genetic disease characterised by renal phosphate wasting, bone mineralisation defects, rickets, abnormal tooth development, poor growth and, often, bone pain. Common treatment of children involves supplementation with oral phosphate and active vitamin D (often termed ‘conventional therapy’). The objective of this study was to identify and understand the perceived limitations of conventional therapy for the treatment of paediatric patients with XLH.

Methods: An insights protocol, comprising a systematic literature review on limitations of conventional therapy (1988–2018) alongside a two-round questionnaire gathering expert paediatric XLH physicians’ opinions, was performed. The open-ended, first-round questionnaire prompted experts to list their perceived limitations of conventional therapy; responses were then coded into ‘items’ using thematic analysis. Experts were subsequently asked to rate their agreement with the inclusion of each item in the final study list (5-point Likert scale). Further ratings were also solicited on the frequency, impact on patients (5-point Likert), and challenge posed to treating physicians (10-point Likert) for each item.

Results: Following the literature review 72 full-text publications were identified, from which 16 items were coded. From the first-round questionnaire 18 items were coded; experts recommended all items for inclusion in the study in the second-round. In total, 23 distinct limitations of conventional therapy covering persistence, convenience and adherence; efficacy; and safety were identified, with 11/23 items identified in both the literature and assessment of paediatric expert opinion. Limitations relating to persistence, convenience and adherence consistently had the tightest agreement of scores across all second-round questions (average ranges: 1.67–4.67), compared with efficacy (2.0–5.2) and safety (1.71–6.29) limitations. When individual items were assessed, inability to normalise serum phosphate levels had the highest combined limitation score – combined frequency, patient impact, and treatment challenge scores – (14/20), followed by inadequate growth normalisation and nephrocalcinosis (13/20); the majority of the next five highest scoring items (12/20) related to adherence, persistence and convenience.

Conclusions: These results provide a better understanding of the limitations of conventional therapy, as well as the basis for a potential framework that could be used to assess new treatment options in the XLH treatment paradigm.

Disclosure: GA has received honoraria/consultancy fees and travel support from Kyowa Kirin Services Ltd. CdLC and ZM has received honoraria/consultancy fees from Kyowa Kirin Services Ltd. RJ is acting in a consultancy/advisory role for Kyowa Kirin Services Ltd.