#2015 Burosumab therapy in adult patients with X-linked hypophosphatemia: a three-year follow-up study
Authors: Rotondi Silverio , Tartaglione Lida , Pasquali Marzia , Cacchioni Carlotta , Tinti Francesca , Perrotta Adolfo Marco , Punzo Alessandra , Lai Silvia , Mazzaferro Sandro 
Published: May 2024

Abstract

Background and Aims
X-linked hypophosphatemic rickets (XLH) arises from mutations in the PHEX gene, resulting in elevated FGF23 levels, renal phosphate loss, hypophosphatemia, low vitamin D, heightened alkaline phosphatase (AP), and associated bone disorders. In challenging the conventional therapy of vitamin D and phosphate supplements, Burosumab, a monoclonal antibody against FGF23, has shown promise in normalizing phosphate and vitamin D levels in pediatric patients. However, its effectiveness in adult patients with established bone lesions remains an area of investigation. This study aims to present the three-year outcomes of Burosumab therapy on both biochemical and clinical aspects in adult XLH patients.

Method
The study assessed the efficacy of Burosumab in adult XLH patients (age &gt;18, drug-naïve) before and continuously over three years post-therapy. Monthly assessments of biochemical parameters (phosphatemia, alkaline phosphatase, Tubular Maximum Reabsorption of Phosphate per Glomerular Filtration Rate, TMP/GFR) were conducted before the monthly administration of Burosumab, while clinical improvements were monitored every six months using established tests, including the six-minute walk test, UP and go timed test, and WOMAC Index. Burosumab was administered monthly at a consistent dosage of 1 mg/kg throughout the entire follow-up period.

Results
In a cohort of five genetically diagnosed XLH patients (average age 45 ± 10 years, average weight 60 ± 10 kg), the average monthly Burosumab dose was 60 ± 10 mg. Baseline values and subsequent changes in Ps, TMP/GFR, WOMAC Index, six-minute walk, and UP and go test are presented in Table 1 and Fig. 1. Importantly, no significant adverse events were reported during the initial year of treatment.

Conclusion
Burosumab therapy demonstrated excellent tolerability and yielded substantial improvements in biochemical parameters (Ps and TMP/GFR), maintaining stability over the entire three-year follow-up. Alkaline phosphatase levels, initially elevated, exhibited a progressive reduction in the second and third years, eventually reaching values within the normal range. Functional indices, reflective of enhanced strength (improved walk test and UP and go timed test) and diminished pain (optimal WOMAC test score), showcased notable improvements in the first year, persisting with stability during the follow-up period, with the exception of the walk test, which demonstrated a gradual and sustained enhancement.
The findings suggest that Burosumab is a well-tolerated and effective therapeutic option for adult XLH patients. The observed reduction in alkaline phosphatase after a year of treatment implies a normalization of bone turnover, while the progressive improvement in the walk test indicates a sustained clinical enhancement likely associated with the chronic positive effects of maintaining biochemical stability.