Safety and Efficacy of Elosulfase Alfa in Australian Patients with Morquio a Syndrome: A Phase 3b Study

Abstract The safety and efficacy of elosulfase alfa were evaluated in a multicenter, open-label, phase 3b study in Australian Morquio A patients, consisting of a 49-week initial phase and an extension phase until elosulfase alfa was government funded. Thirteen patients (1-27 years) were enrolled. No new safety concerns were identified over 138 weeks. Most drug-related adverse events were mild or moderate in severity; none led to study discontinuation. After 49 weeks of treatment, median improvements from baseline were seen in the 6-minute walk test (+41.0 m), 3-minute stair climb test (+14.0 stairs/min), forced vital capacity (+16.4%), forced expiratory volume in 1 second (+14.1%), urine keratan sulfate (-7.1 µg/mg creatinine), and pain intensity. Growth, cardiac function, sleep, and quality of life results were mixed or stable. These results provide further evidence of the acceptable safety/tolerability profile of elosulfase alfa. The improvements in endurance, pulmonary function, and pain support findings from previous studies.

Hypermobility and Musculoskeletal Pain in Adolescents.

OBJECTIVE: To determine the prevalence of generalized joint hypermobility (GJH) in a large cohort of Australian children and determine the associations between GJH and musculoskeletal pain. STUDY DESIGN: This is a cross-sectional analysis of the Western Australian Pregnancy Cohort (Raine) Study. Hypermobility was measured in 1584 participants at 14 years of age using the Beighton scoring system, along with a range of other factors including musculoskeletal pain status. Logistic regression models were used to assess independent associations of GJH with factors of interest. RESULTS: The prevalence of GJH was 60.6% and 36.7% in girls and boys, respectively, when defined as a Beighton score of ≥4; when defined as ≥6, it was 26.1% and 11.5%. In girls, positive associations between GJH and higher socioeconomic status and better motor competence were observed. In boys, positive associations between GJH and lower body mass index were observed. After adjusting for potential confounders, an association between number of pain areas in the last month and made worse with sport were identified in boys but not girls. CONCLUSION: The high prevalence rates of GJH as defined by commonly used Beighton cutoff values in this cohort highlight the need to question the appropriateness of these cutoffs in future studies. Future prospective studies of the association between GJH and musculoskeletal pain should be adjusted for confounding variables identified in this study, and be powered for sex-specific analyses owing to the differing prevalence rates and hypermobility correlates in male and female samples.