Respiratory function during enzyme replacement therapy in late-onset Pompe disease: longitudinal course, prognostic factors, and the impact of time from diagnosis to treatment start.

OBJECTIVE: To examine respiratory muscle function among late-onset Pompe disease (LOPD) patients in the Pompe Registry (NCT00231400/Sanofi Genzyme) during enzyme replacement therapy (ERT) with alglucosidase alfa by assessing the longitudinal course of forced vital capacity (FVC), prognostic factors for FVC, and impact of time from diagnosis to ERT initiation. METHODS: Longitudinal FVC data from LOPD (symptom onset > 12 months or ≤ 12 months without cardiomyopathy) patients were analyzed. Patients had to have baseline FVC (percent predicted upright) assessments at ERT start and ≥ 2 valid post-baseline assessments. Longitudinal analyses used linear mixed-regression models. RESULTS: Among 396 eligible patients, median baseline FVC was 66.9% (range 9.3-126.0). FVC remained stable during the 5-year follow-up (slope = - 0.17%, p = 0.21). Baseline FVC was lower among various subgroups, including patients who were male; older at ERT initiation; had a longer duration from symptom onset to ERT initiation; and had more advanced disease at baseline (based on respiratory support use, inability to ambulate, ambulation device use). Age at symptom onset was not associated with baseline degree of respiratory dysfunction. Differences between subgroups observed at baseline remained during follow-up. Shorter time from diagnosis to ERT initiation was associated with higher FVC after 5 years in all patients and the above subgroups using a cut-off of 1.7 years. CONCLUSION: FVC stability over 5 years suggests that respiratory function is preserved during long-term ERT in real-world settings. Early initiation of alglucosidase alfa was associated with preservation of FVC in LOPD patients with better respiratory function at the time of treatment initiation.

Source document verification in the Mucopolysaccharidosis Type I Registry.

PURPOSE: The Mucopolysaccharidosis Type I (MPS I) Registry is an international observational database that tracks the natural history and the outcomes of patients with MPS I. The Registry was a regulatory requirement following the approval of laronidase enzyme replacement therapy for MPS I in 2003. All data are collected voluntarily after informed consent from the patient or family. Data are checked through queries, monthly reviews, and electronic audits to identify missing, inconsistent, or invalid data. This analysis sought to determine overall data accuracy in the Registry through source document verification (SDV). METHODS: Two phases of SDV were performed. In each phase, Registry data were compared against source documents at sites in Europe, Latin America, and North America. Three patients were randomly selected for SDV at each of the selected sites among all patients enrolled ≥18 months and ever receiving laronidase. Key parameters central to MPS I and its treatment were examined from the baseline and the last available assessments. RESULTS: Results indicate an overall source-to-database error rate in the MPS I Registry of 2.7% (47 discrepancies out of 1715 items; 95% confidence interval [2.2%, 3.5%]) in Phase 1 and 3.7% (64 discrepancies out of 1732 items; 95% confidence interval [2.9%, 4.7%]) in Phase 2. No systematic errors were found. CONCLUSIONS: The overall error rates in both phases of SDV demonstrate acceptable data accuracy in the MPS I Registry within the data fields that were assessed. Copyright © 2011 John Wiley & Sons, Ltd.