Evaluation of the long-term treatment effects of idursulfase using statistical modelling: Data from the Hunter Outcome Survey (HOS)

Treatment for mucopolysaccharidosis type II (MPS II Hunter syndrome) is available in the form of intravenous enzyme replacement therapy (ERT) with idursulfase (Shire, Lexington, MA, USA). This analysis used statistical modelling to evaluate the long-term treatment effects of idursulfase on selected clinical parameters based on data from HOS, a global, observational registry (Shire, Lexington, MA, USA). Mixed modelling was used to analyse data from male patients followed prospectively in HOS who had received idursulfase for 5-8 years and information available for two or more timepoints, of which one was pre-ERT. Data were excluded from patients with only pre-ERT information available, who ha…

Cervical spine pathology in Hunter syndrome: Data from the Hunter Outcome Survey

Longitudinal analysis of endurance and respiratory function from a natural history study of Morquio A syndrome

Objectives: Baseline data from the Morquio A Clinical Assessment Program (MorCAP) revealed that individuals with Morquio A syndrome show substantial impairment in multiple domains including endurance and respiratory function (Harmatz et al., Mol Genet Metab, 2013). Here, 1- and 2-year longitudinal endurance and respiratory function data are presented.Methods: Endurance was assessed using the 6-minute walk test (6MWT) and the 3-minute stair climb test (3MSCT). Respiratory function was evaluated by measuring forced vital capacity (PVC) and maximum voluntary ventilation (MW). Data were analyzed using repeated measures ANCOVA models. Annualized estimates of change were determined using model es…

Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), …

The Morquio A Clinical Assessment Program: Baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects

Abstract Objectives The objectives of this study are to quantify endurance and respiratory function and better characterize spectrum of symptoms and biochemical abnormalities in mucopolysaccharidosis IVA subjects. Methods MorCAP was a multicenter, multinational, cross sectional study amended to be longitudinal in 2011. Each study visit required collection of medical history, clinical assessments, and keratan sulfate (KS) levels. Results Data from the first visit of 325 subjects (53% female) were available. Mean age was 14.5 years. Mean ± SD height z-scores were − 5.6 ± 3.1 as determined by the CDC growth charts. Mean ± SD from the 6-minute-walk-test was 212.6 ± 152.2 m, revealing limitation…

Characteristics of patients with mucopolysaccharidosis type II who have received a bone marrow transplant: Data from the Hunter Outcome Survey

Mucopolysaccharidosis type II (MPS II Hunter syndrome) is a rare, life-limiting, X-linked lysosomal storage disease. The Hunter Outcome Survey (HOS) is a Shire-sponsored, global, observational registry initiated in 2005 that collects real-world data on the natural history of MPS II and long-term treatment with enzyme replacement therapy (ERT) with idursulfase. Patients receiving other forms of pharmacological ERT are excluded from HOS but individuals who have received a bone marrow transplant (BMT) may be enrolled. This analysis examined the characteristics of 36 male patients in HOS from Europe and North America who had received a BMT (March 2018 data). In total, 22 patients (61.1%) were E…

A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency

BackgroundLysosomal acid lipase is an essential lipid-metabolizing enzyme that breaks down endocytosed lipid particles and regulates lipid metabolism. We conducted a phase 3 trial of enzyme-replacement therapy in children and adults with lysosomal acid lipase deficiency, an underappreciated cause of cirrhosis and severe dyslipidemia. MethodsIn this multicenter, randomized, double-blind, placebo-controlled study involving 66 patients, we evaluated the safety and effectiveness of enzyme-replacement therapy with sebelipase alfa (administered intravenously at a dose of 1 mg per kilogram of body weight every other week); the placebo-controlled phase of the study was 20 weeks long and was followe…

A multinational, multidisciplinary consensus for the diagnosis and management of spinal cord compression among patients with mucopolysaccharidosis VI.

Cervical cord compression is a sequela of mucopolysaccharidosis VI, a rare lysosomal storage disorder, and has devastating consequences. An international panel of orthopedic surgeons, neurosurgeons, anesthesiologists, neuroradiologists, metabolic pediatricians, and geneticists pooled their clinical expertise to codify recommendations for diagnosing, monitoring, and managing cervical cord compression; for surgical intervention criteria; and for best airway management practices during imaging or anesthesia. The recommendations offer ideal best practices but also attempt to recognize the worldwide spectrum of resource availability. Functional assessments and clinical neurological examinations …

A multi-national, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of BMN 110 treatment for mucopolysaccharidosis IVA (Morquio syndrome type A)