This post hoc analysis applied the Projected Retained Ability Score (PRAS) methodology to Differential Ability Scales-II General Conceptual Ability (DAS-II GCA) scores obtained from patients with neuronopathic mucopolysaccharidosis II (MPS II, Hunter syndrome) treated with intrathecal idursulfase (idursulfase-IT) in a phase 2/3 randomized trial (NCT02055118) and extension (NCT02412787). Patients were randomized to receive idursulfase-IT or no idursulfase-IT (year 1); all patients received idursulfase-IT during the extension (year 2). The DAS-II GCA score measures cognitive ability relative to a same-aged normative sample. The PRAS allows assessment of absolute changes in cognitive ability instead of changes in age-based norm scores. Patients with baseline, 1- and 2-year DAS-II assessments were categorized into cognitive development groups as above average, average, below average, stabilized or deteriorating development. Proportions of patients and changes in mean GCA scores within these groups were assessed and compared at years 1 and 2 for early versus delayed idursulfase-IT. At 1 year, proportions of patients in the idursulfase-IT (n=29) versus no idursulfase-IT (n=15) groups with above average, average, below average, stabilized or deteriorating cognitive development were 7.0% versus 0%, 66% versus 53%, 0% versus 0%, 21% versus 27% and 7% versus 20%, respectively. At 2 years, proportions of patients in the early idursulfase-IT (n=27) versus delayed idursulfase-IT (n=12) groups with above average, average, below average, stabilized or deteriorating cognitive development were 4% versus 0%, 44% versus 42%, 4% versus 8%, 37% versus 42% and 11% versus 8%, respectively. Differences between treatment groups appeared more pronounced at year 1 than at year 2, with a greater proportion of idursulfase-IT patients having above average or average cognitive ability compared with no idursulfase-IT patients. Further investigation of the utility of PRAS methodology in describing development trajectories and treatment response in MPS II is warranted. Shire (a Takeda company) funded this study and writing support.
