Evaluation of the long-term treatment efects of intravenous idursulfase in patients with mucopolysaccharidosis II (MPS II) using statistical modeling : data from the Hunter Outcome Survey (HOS)

• Autor(a) principal: Muenzer, Joseph
• Data de Publicação: 2021
• Outros Autores: Botha, Jaco, Harmatz, Paul, Giugliani, Roberto, Kampmann, Christoph, Burton, Barbara K.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/234528
• topic: Mucopolissacaridose II; Doenças por armazenamento dos lisossomos; Modelos estatísticos; Prognóstico; Tratamento farmacológico; Terapia de reposição de enzimas; Mucopolysaccharidosis II; MPS II; Hunter syndrome; Lysosomal storage disease; Statistical modeling; Disease registry; Idursulfase; Enzyme replacement therapy

Background: Mucopolysaccharidosis II (MPS II; Hunter syndrome) is a rare, life-limiting lysosomal storage disease caused by defcient iduronate-2-sulfatase activity. Enzyme replacement therapy (ERT) with intravenous (IV) idursulfase can stabilize or improve many somatic manifestations, but there remains a need for further analysis of long-term treatment outcomes. Using data from patients with MPS II enrolled in the Hunter Outcome Survey (HOS), mixed modeling was performed to evaluate and predict the efects of IV idursulfase treatment on selected clinical parameters for up to 8 years following treatment start. The modeling population comprised male patients followed prospectively in HOS who had received IV idursulfase for at least 5 years and who had data available for two or more time points (at least one post-ERT). Age at ERT start and time since ERT start were included as covariates. Results: In total, 481 patients were eligible for inclusion in at least one model. At 8 years post-ERT start, improvement from baseline was predicted for each age group (<18 months, 18 months to<5 years and≥5 years at treatment start) in the following parameters: mean urinary glycosaminoglycan levels (percentage changes of>–75% in each group), mean left ventricular mass index (decreases of~1 g/m2 ) and mean palpable liver size (decreases of>2 cm). Improvements in mean 6-min walk test distance (increase of>50 m) and stabilization in percent predicted forced vital capacity and forced expiratory volume in 1 s (decreases of~4 and~9 percentage points, respectively) at 8 years post-ERT start were predicted for patients aged≥5 years at ERT start (these assessments are unsuitable for patients aged<5 years). Predicted changes over time were similar across the three age groups; however, overall outcomes were most favorable in children aged<18 months at ERT start. Conclusions: These fndings suggest that the previously reported positive efects of IV idursulfase on the somatic manifestations of MPS II are predicted to be maintained for at least 8 years following ERT initiation and highlight the value of statistical modeling to predict long-term treatment outcomes in patients with rare diseases.