Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome

Abstract

Purpose: This study evaluated the safety and effectiveness of long-term enzyme replacement therapy with idursulfase (recombinant human iduronate-2-sulfatase) in patients with Hunter syndrome. Methods: All 94 patients who completed a 53-week double-blinded study of idursulfase enrolled in this open-labeled extension study and received intravenous idursulfase at a dose of 0.5 mg/kg weekly for 2 years, and clinical outcomes and safety were assessed. Results: No change in percent predicted forced vital capacity was seen, but absolute forced vital capacity demonstrated sustained improvement and was increased 25.1% at the end of the study. Statistically significant increases in 6-minute walking test distance were observed at most time points. Mean liver and spleen volumes remained reduced throughout the 2-year extension study. Mean joint range of motion improved for the shoulder and remained stable in other joints. Both the parent-and child-assessed Child Health Assessment Questionnaire Disability Index Score demonstrated significant improvement. Infusion-related adverse events occurred in 53% of patients and peaked at Month 3 of treatment and declined thereafter. Neutralizing IgG antibodies were detected in 23% of patients and seemed to attenuate the improvement in pulmonary function. Conclusions: Weekly infusions of idursulfase result in sustained clinical improvement during 3 years of treatment. Genet Med 2011:13(2):95-101.

Obstructive Sleep Apnea Syndrome in Children With Type Ii Mucopolysaccharidosis (Hunter Syndrome)

“…Comparison of average AHI, SpO 2 and DI values did not reveal effect of adenoidal hypertrophy on the OSAS severity (approximately the same percentage of mild, moderate and severe OSAS in all the groups); we did not reveal significant differences in SpO 2 and DI values in all the groups either (p>0.05; see tb. 10).…”

“…Two children with severe Hunter syndrome underwent the second trial 2 years after beginning of ERT. The first patient (9 years of age at the beginning of the study, 11 years -the second trial) had considerable positive dynamics of AHI, SpO 2 and DI values (before the therapy AHI was 4.4, SpO 2 -88%; after 2 years AHI was 0.6, SpO 2 -95.6%); no significant dynamics was observed in the second patients due to absence of OSAS before or in the setting of the ERT (before the therapy AHI was 0.8, SpO 2 -97%; after 2 years AHI was 0.0, SpO 2 -95%). Positive effect of enzyme replacement therapy was demonstrated in the 6-minute-long walk test and by pulmonary function assessment.…”

“…7). 2 and DI values in children with Hunter syndrome. OSAS was revealed in 5 out of 9 (55.6%) children with adenoidal hypertrophy: mild -in 2 patients (22.2%), moderate -in 2 patients (22.2%), severe -in 1 patient (11.1%) (tb.…”

“…The overwhelming majority of patients of both groups had SpO 2 lower than 95% (mild form -71.4%, 5 out of 7; severe form -80%, 8 out of 10). We defined the average AHI, SpO 2 and DI values in children with different tracheobronchial tree lesions (tb. 6, 7).…”

“…Motion incoordination develops at 3-4 years of age along with behavior changes and development of aggressiveness. Deafness, joint stiffness, contractures and large and small joints, atypical pigment retinitis and corneal opacity appear at an older age [2][3][4]. The ongoing cellular accumulation of glycosaminoglycans results in affection of vital organs and their progressive functional deterioration: development of secondary cardiomyopathy, incompetence and/or stenosis of mitral and aortic valves, obstructive respiratory tract diseases (including obstructive sleep apnea syndrome furthered by tonsillar and adenoidal hypertrophy, tracheal lumen narrowing, tracheomalacia, thickening of vocal cords, macroglossia), hepatosplenomegaly; psychoverbal development delay with subsequent mental retardation.…”