Conclusion
deteriorating cognitive functioning, early-onset cognitive impairment, neuronopathic MPS II
GCA
The results from this analysis demonstrate that application of PRAS methodology to DAS-II GCA scores can be used to characterize change in cognitive functioning more specifically in patients with early-onset cognitive impairment reporting a decrease in norm-based scores. PRAS methodology allowed differentiation of patients who were considered to have below-average improvement in cognitive functioning (i.e., declines in GCA scores) into three separate categories reflecting absolute change in cognitive functioning (below-average cognitive development, plateauing cognitive functioning, and deteriorating cognitive functioning). Following 1 year of treatment with idursulfase-IT, a greater proportion of patients had above-average or average cognitive growth rate compared with those who had not received idursulfase-IT treatment, and a smaller proportion of patients who had received idursulfase-IT showed deteriorating cognitive functioning, particularly in patients younger than 6 years of age at phase 2/3 baseline. The differences between treatment groups were less pronounced at 2 years than at 1 year. Compared with a previously reported categorical analysis of the trial data, in which a high proportion of patients younger than 6 years of age at phase 2/3 baseline were categorized as having below-average cognitive development after treatment (reflected by a decline in DAS-II GCA scores), the present analysis demonstrated that only a small proportion of these patients actually had below-average cognitive growth rates in DAS-II GCA scores and, importantly, that the majority had plateauing cognitive functioning and remained in the same cognitive category. These results support further investigation into the role of PRAS methodology in assessing cognitive functioning over time in patients with neuronopathic MPS II.