TY - CHAP
T1 - Cardiopulmonary exercise testing reflects improved exercise capacity in response to treatment in morquio a patients
T2 - Results of a 52-week pilot study of two different doses of elosulfase alfa
AU - Berger, Kenneth I.
AU - Burton, Barbara K.
AU - Lewis, Gregory D.
AU - Tarnopolsky, Mark
AU - Harmatz, Paul R.
AU - Mitchell, John J.
AU - Muschol, Nicole
AU - Jones, Simon A.
AU - Sutton, V. Reid
AU - Pastores, Gregory M.
AU - Lau, Heather
AU - Sparkes, Rebecca
AU - Shaywitz, Adam J.
N1 - Funding Information:
Acknowledgments The authors are grateful to Ismar Healthcare NV for their assistance in the writing of the manuscript, which was funded by BioMarin Pharmaceutical Inc. Fred Genter is acknowledged for his work as a statistician for the study.
Funding Information:
This study was sponsored by BioMarin Pharmaceutical Inc. and supported, in part, by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through UCSF-CTSI Grant Number UL1 TR000004 (Dr. Harmatz). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Support in the process of manuscript development was also funded by BioMarin Pharmaceutical Inc.
PY - 2018
Y1 - 2018
N2 - Objective: To assess impact of a 52-week elosulfase alfa enzyme replacement therapy (ERT) on exercise capacity in Morquio A patients and analyze cardiorespiratory and metabolic function during exercise to uncover exercise limitations beyond skeletal abnormalities. Methods: Morquio A patients aged ≥7 years, able to walk >200 m in the 6-minute walk test (6MWT), received elosulfase alfa 2.0 mg/kg/week (N = 15) or 4.0 mg/kg/week (N = 10) for 52 weeks in the randomized, double-blind MOR-008 study (ClinicalTrials.gov NCT01609062) and its extension. Exercise capacity was assessed by 6MWT, 3-minute stair climb test (3MSCT), and cardiopulmonary exercise test (CPET; N = 15 dosage groups combined). Results: Changes over 52 weeks in 6MWT and 3MSCT were minimal. Baseline CPET results showed impaired weight-adjusted peak oxygen uptake (VO2), partly attributable to inability to increase tidal volume during exercise. CPET measures of exercise function showed significant improvement at 25 and/or 52 weeks in exercise duration, peak workload, O2 pulse, and peak tidal volume (% increases in duration, 16.9 (P = 0.0045) and 9.4 (P = 0.0807); peak workload, 26.5 (P = 0.0026) and 21.2 (P = 0.0132); O2 pulse, 10.7 (P = 0.0187) and 2.3 (P = 0.643); peak tidal volume, 11.7 (P = 0.1117) and 29.1 (P = 0.0142)). In addition, decreased VO2/work ratio was noted (% decrease −7.6 [−11.9, 1.3] and −9.2 [−25.7, 5.1]), indicating performance of work at reduced oxygen cost. Conclusions: CPET uncovers limitation in exercise capacity in Morquio A related to reduced lung function. ERT improves exercise capacity and efficiency of oxygen utilization, not attributable to changes in cardiac or pulmonary function. Further study of the long-term impact of ERT on exercise capacity and the clinical relevance of the observed changes is warranted.
AB - Objective: To assess impact of a 52-week elosulfase alfa enzyme replacement therapy (ERT) on exercise capacity in Morquio A patients and analyze cardiorespiratory and metabolic function during exercise to uncover exercise limitations beyond skeletal abnormalities. Methods: Morquio A patients aged ≥7 years, able to walk >200 m in the 6-minute walk test (6MWT), received elosulfase alfa 2.0 mg/kg/week (N = 15) or 4.0 mg/kg/week (N = 10) for 52 weeks in the randomized, double-blind MOR-008 study (ClinicalTrials.gov NCT01609062) and its extension. Exercise capacity was assessed by 6MWT, 3-minute stair climb test (3MSCT), and cardiopulmonary exercise test (CPET; N = 15 dosage groups combined). Results: Changes over 52 weeks in 6MWT and 3MSCT were minimal. Baseline CPET results showed impaired weight-adjusted peak oxygen uptake (VO2), partly attributable to inability to increase tidal volume during exercise. CPET measures of exercise function showed significant improvement at 25 and/or 52 weeks in exercise duration, peak workload, O2 pulse, and peak tidal volume (% increases in duration, 16.9 (P = 0.0045) and 9.4 (P = 0.0807); peak workload, 26.5 (P = 0.0026) and 21.2 (P = 0.0132); O2 pulse, 10.7 (P = 0.0187) and 2.3 (P = 0.643); peak tidal volume, 11.7 (P = 0.1117) and 29.1 (P = 0.0142)). In addition, decreased VO2/work ratio was noted (% decrease −7.6 [−11.9, 1.3] and −9.2 [−25.7, 5.1]), indicating performance of work at reduced oxygen cost. Conclusions: CPET uncovers limitation in exercise capacity in Morquio A related to reduced lung function. ERT improves exercise capacity and efficiency of oxygen utilization, not attributable to changes in cardiac or pulmonary function. Further study of the long-term impact of ERT on exercise capacity and the clinical relevance of the observed changes is warranted.
KW - Cardiopulmonary exercise test
KW - Elosulfase alfa
KW - Endurance
KW - Enzyme replacement therapy
KW - Exercise capacity
KW - Mucopolysaccharidosis IVA
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U2 - 10.1007/8904_2017_70
DO - 10.1007/8904_2017_70
M3 - Chapter
C2 - 29159458
AN - SCOPUS:85044445484
T3 - JIMD Reports
SP - 9
EP - 17
BT - JIMD Reports
PB - Springer
ER -