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

Abstract

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 had received a bone marrow transplant or had enrolled in an idursulfase clinical trial. Age at and time since ERT start were included as covariates and results were modelled for up to 8 years of treatment. For the prediction of percent-predicted forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and the 6-minute walk test (6MWT), only data from patients aged ≥5 years and without cognitive impairment were used. A sensitivity analysis assessed robustness of the model using information from patients with data for five or more timepoints. The main model indicated a decrease over time in urinary glycosaminoglycan levels and palpable liver size. Left ventricular mass index was stable for up to 8 years of treatment while there was a slight decrease in percent-predicted FVC and FEV1 and a gradual increase in distance walked in the 6MWT. Similar results were observed in the sensitivity analysis, indicating that this model provides reliable estimates. The nature of this analysis means that these findings are descriptive only. However, our results support those of previous studies and indicate that idursulfase has a positive effect on somatic manifestations of MPS II. Shire sponsors HOS and funds medical writing support.