Hendriksz, Christian J.Parini, RossellaAlSayed, Moeenaldeen D.Raiman, JulianGiugliani, RobertoMitchell, John J.Burton, Barbara K.Guelbert, NorbertoStewart, Fiona J.Hughes, Derralynn A.Matousek, RobertHawley, Sara M.Decker, CelesteHarmatz, Paul R.2018-04-192018-04-192018-02Hendriksz, C.J., Parini, R., AlSayed, M.D. et al. 2018, 'Impact of long-term elosulfase alfa on activities of daily living in patients with Morquio a syndrome in an open-label, multi-center, phase 3 extension study', Molecular Genetics and Metabolism, vol. 123, no. 2, pp. 127-134.1096-7192 (print)1096-7206 (online)10.1016/j.ymgme.2017.11.015http://hdl.handle.net/2263/64650Supplementary file 1. Items in the MPS Health Assessment Questionnaire (MPS-HAQ).Supplementary file 2. Items in the MPS Health Assessment Questionnaire (MPS-HAQ) (A) showing impairment in the self-care and mobility domains (score ≥ 1) and the caregiver-assistance domain (score > 1) in ≥ 70% of patients and (B) scored “unable to complete” or “complete assistance required” in ≥ 15% of patients in the MOR-005 ITT population.Supplementary file 3. Baseline demographics of patients from the MOR-005 intent-to-treat (ITT) and modified per-protocol (MPP) population and comparable patients from the MorCAP natural history study included in the 2-year analysis.BACKGROUND : Long-term safety and efficacy of elosulfase alfa enzyme replacement therapy (ERT) were assessed in 173 patients with Morquio A syndrome (mucopolysaccharidosis IVA) in a 96-week, open-label, multi-center, phase 3 extension study (MOR-005) of the pivotal 24-week, placebo-controlled study (MOR-004). Changes in efficacy endpoints were evaluated over 120 weeks, from MOR-004 baseline to MOR-005 week 96. We report the impact of ERT on activities of daily living (ADL) across three domains (mobility, self-care, and caregiver-assistance), as assessed by the Mucopolysaccharidosis Health Assessment Questionnaire (MPS-HAQ) after 72 and 120 weeks or approximately 1 and 2 years. RESULTS : Mean baseline MPS-HAQ domain scores showed impairments in mobility, self-care, and independence. The MOR-005 intent-to-treat population (ITT; N =169, including 158 with 2 years follow-up) showed sustained significant reductions (representing improvements) in mobility and self-care domain least square (LS) mean scores vs. baseline at 1 and 2 years and a non-significant decrease in the caregiver-assistance domain at 2 years. At week 120, LS mean (SE) changes from baseline were−0.5 (0.1) for mobility (P =0.002),−0.4 (0.1) for selfcare (P =0.001), and −1.0 (0.5) for caregiver-assistance (P= 0.06) (ITT population). Improvements in MPSHAQ domain scores vs. baseline at 1 and 2 years were greater in patients continuously treated with the weekly dosing regimen than in the total MOR-005 population and statistically significant across domains. A comparable untreated cohort of patients from the Morquio A Clinical Assessment Program (MorCAP) natural history study (ITT population, N =94, including 37 with 2 years follow-up) showed no improvement over 2 years, with two of the three domains worsening (LS mean (SE) changes from baseline: 0.3 (0.3) for mobility, 0.4 (0.2) for self-care, −0.5 (0.8) for caregiver-assistance). Changes in LS mean scores vs. baseline were statistically significantly different between MOR-005 and MorCAP for the mobility domain (−0.7 (SE 0.4), P=0.0490) and the self-care domain (−0.7 (SE 0.3), P=0.0146) at 2 years.en© 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).Morquio A syndromeElosulfase alfaDisabilityActivities of daily living (ADL)Enzyme replacement therapy (ERT)DiseaseEnduranceSafetyRespiratory functionMucopolysaccharidosis IVAMucopolysaccharidosis (MPS)Article