Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease
Bibliographic record
Abstract
Emerging phenotypes in long-term survivors with Pompe disease on standard enzyme replacement therapy (ERT) (alglucosidase alfa 20 mg/kg/2 weeks) can include patients with worsening motor function. Whether higher doses of ERT improve skeletal function in these patients has not been systematically studied. This exploratory, randomized, open-label, 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa (20 mg/kg/week or 40 mg/kg/2 weeks) in 13 patients with Pompe disease and clinical decline or a lack of improvement on standard ERT: late-onset (n = 4), infantile-onset (n = 9). Cross-reactive immunologic material assay-negative patients were excluded. Eleven of 13 patients completed the study. Trends for improvement were seen in total gross motor function, but not mobility; however, 6 (late-onset, 2; infantile-onset, 4) of 11 patients (55%) who met the entry criteria of motor decline (late-onset, 4; infantile-onset, 7) showed improvement in motor and/or mobility skills. No between-regimen differences in efficacy emerged. Two case studies highlight the benefits of increased ERT dose in patients with Pompe disease experiencing clinical decline. Both alternative regimens were generally well tolerated. This study was limited by the small sample size, which is not uncommon for small clinical studies of rare diseases. Additionally, the study did not include direct assessment of muscle pathology, which may have identified potential causes of decreased response to ERT. Results were inconclusive but suggest that increased ERT dose may be beneficial in some patients with Pompe disease experiencing motor decline. Controlled studies are needed to clarify the benefits and risks of this strategy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".