Respiratory function during enzyme replacement therapy in late-onset Pompe disease: longitudinal course, prognostic fact
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ORIGINAL COMMUNICATION
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 David W. Stockton1 · Priya Kishnani2 · Ans van der Ploeg3 · Juan Llerena Jr.4 · Matthias Boentert5 · Mark Roberts6 · Barry J. Byrne7 · Roberto Araujo8 · Sonia S. Maruti8 · Nathan Thibault8 · Karien Verhulst9 · Kenneth I. Berger10 Received: 22 January 2020 / Revised: 15 May 2020 / Accepted: 19 May 2020 © The Author(s) 2020
Abstract 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 postbaseline 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. Keywords Pompe disease · Late-onset Pompe disease · Respiratory function · Enzyme replacement therapy · Alglucosidase alfa · Registry Sonia S. Maruti is affiliation at the time of the analysis and development of the manuscript (Sanofi Genzyme, Cambridge, MA). Current affiliation is Boehringer Ingelheim. * David W. Stockton [email protected] 1
Division of Genetic, Genomic and Metabolic Disorders, Departments of Pediatrics and Internal Medicine, Wayne State University and Children’s Hospital of Michigan, Detroit, MI, USA
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
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3
Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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Depa
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