Abstract
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.
| Original language | English (US) |
|---|---|
| Title of host publication | JIMD Reports |
| Publisher | Springer |
| Pages | 9-17 |
| Number of pages | 9 |
| DOIs | |
| State | Published - Jan 1 2018 |
Publication series
| Name | JIMD Reports |
|---|---|
| Volume | 42 |
| ISSN (Print) | 2192-8304 |
| ISSN (Electronic) | 2192-8312 |
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Keywords
- Cardiopulmonary exercise test
- Elosulfase alfa
- Endurance
- Enzyme replacement therapy
- Exercise capacity
- Mucopolysaccharidosis IVA
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
Cite this
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Cardiopulmonary exercise testing reflects improved exercise capacity in response to treatment in morquio a patients : Results of a 52-week pilot study of two different doses of elosulfase alfa. / Berger, Kenneth I.; Burton, Barbara K; Lewis, Gregory D.; Tarnopolsky, Mark; Harmatz, Paul R.; Mitchell, John J.; Muschol, Nicole; Jones, Simon A.; Sutton, V. Reid; Pastores, Gregory M.; Lau, Heather; Sparkes, Rebecca; Shaywitz, Adam J.
JIMD Reports. Springer, 2018. p. 9-17 (JIMD Reports; Vol. 42).Research output: Chapter in Book/Report/Conference proceeding › Chapter
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.
PY - 2018/1/1
Y1 - 2018/1/1
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
UR - http://www.scopus.com/inward/record.url?scp=85044445484&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044445484&partnerID=8YFLogxK
U2 - 10.1007/8904_2017_70
DO - 10.1007/8904_2017_70
M3 - Chapter
T3 - JIMD Reports
SP - 9
EP - 17
BT - JIMD Reports
PB - Springer
ER -