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
Bibliographic record
Abstract
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 120weeks, 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 120weeks or approximately 1 and 2years. 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 2years follow-up) showed sustained significant reductions (representing improvements) in mobility and self-care domain least square (LS) mean scores vs. baseline at 1 and 2years and a non-significant decrease in the caregiver-assistance domain at 2years. At week 120, LS mean (SE) changes from baseline were -0.5 (0.1) for mobility (P=0.002), -0.4 (0.1) for self-care (P=0.001), and -1.0 (0.5) for caregiver-assistance (P=0.06) (ITT population). Improvements in MPS-HAQ domain scores vs. baseline at 1 and 2years 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 2years follow-up) showed no improvement over 2years, 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 2years. CONCLUSIONS: Together, these findings suggest that long-term elosulfase alfa ERT is associated with partial recovery of functional abilities, improving Morquio A patients' abilities to perform ADL. TRIAL REGISTRATION: ClinicalTrials.govNCT01415427. Registered 8 August 2011, retrospectively registered.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".