Journal Article

A post hoc analysis of Projected Retained Ability Scores (PRAS) for the longitudinal assessment of cognitive functioning in patients with neuronopathic mucopolysaccharidosis II receiving intrathecal idursulfase-IT

Chirila, Costel, Yee, Karen S., Kronenberger, William G., Mladsi, Deirdre, Barnett, Christine, Davenport, Eric

2023

Overview

Background Norm-based scores used to assess cognitive ability have clinical value when describing functioning of patients with neuronopathic disorders compared with unaffected, same-age peers. However, they have limitations when used to assess change in cognitive ability between two timepoints, especially in children with severe cognitive decline. Calculation of Projected Retained Ability Scores (PRAS) is a novel method developed to characterize absolute change in norm-based ability test scores. In this analysis, PRAS were calculated post hoc for children with mucopolysaccharidosis II (MPS II; Hunter syndrome) and early cognitive impairment in a 52-week phase 2/3 randomized controlled trial (RCT) and its extension study of intrathecal idursulfase (idursulfase-IT). Patients completing the first year of the extension after receiving idursulfase-IT in the RCT and extension (n = 32 of 34 enrolled) or the extension only (n = 15 of 15 enrolled) were categorized according to changes in Differential Ability Scales, Second Edition, General Conceptual Ability (DAS-II GCA) scores and PRAS at 1 and 2 years. Analyses were conducted in the overall population and a subpopulation aged < 6 years at baseline (idursulfase-IT in the RCT and extension [n = 27] and extension only [n = 12]). Results PRAS methodology differentiated patients with decreases in DAS-II GCA scores into three separate categories reflecting below-average cognitive growth rates, plateauing cognitive development, and deteriorating cognitive functioning. After 1 year in the RCT, 72.4% of patients who initiated idursulfase-IT had above-average or average cognitive growth rates in DAS-II GCA scores compared with 53.3% of those who did not receive idursulfase-IT; 6.9% versus 20.0% experienced deteriorating cognitive functioning. Similar results were seen in children aged < 6 years: 76% (idursulfase-IT group) versus 50% (no idursulfase-IT) had above-average or average cognitive growth rates in DAS-II GCA scores; 4% versus 17% had deteriorating cognitive functioning. The difference in the distributions of cognitive categories at 1 year in children aged < 6 years was significant ( p  = 0.048). At 2 years, the proportions of patients in different cognitive categories were more similar between treatment groups. Conclusions PRAS methodology may help to differentiate changes in cognitive development in MPS II, and therefore may represent a valuable addition to existing approaches for interpreting changes in cognitive scores over time. Trial Registration : ClinicalTrials.gov NCT02055118 (registration date: 4 February 2014) and NCT02412787 (registration date: 9 April 2015).

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Age / Analysis / Care and treatment / Child / Children / Children & youth / Cognition / Cognitive ability / Cognitive development / Comparative analysis / Diagnosis / Enzyme Replacement Therapy - methods / Enzymes / Genetic disorders / Growth rate / Human Genetics / Humans / Hunter syndrome / Iduronate Sulfatase - therapeutic use / Idursulfase / Lysosomal storage diseases / Medical research / Medicine / Medicine & Public Health / Metabolic disorders / Mucopolysaccharidosis / Mucopolysaccharidosis II / Mucopolysaccharidosis II - drug therapy / Neuronopathic / Norms / Patients / Pharmacology/Toxicology / Projected Retained Ability Score / Rare diseases