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

Kenneth I. Berger*, Barbara K Burton, Gregory D. Lewis, Mark Tarnopolsky, Paul R. Harmatz, John J. Mitchell, Nicole Muschol, Simon A. Jones, V. Reid Sutton, Gregory M. Pastores, Heather Lau, Rebecca Sparkes, Adam J. Shaywitz

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

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 languageEnglish (US)
Title of host publicationJIMD Reports
PublisherSpringer
Pages9-17
Number of pages9
DOIs
StatePublished - Jan 1 2018

Publication series

NameJIMD Reports
Volume42
ISSN (Print)2192-8304
ISSN (Electronic)2192-8312

Fingerprint

Exercise
Stairs
Testing
Oxygen
Enzyme Replacement Therapy
Tidal Volume
Enzymes
Therapeutics
Workload
Pulse
Lung
human GALNS protein
Clostridium perfringens epsilon-toxin
Exercise Test
Costs
Weights and Measures
Costs and Cost Analysis
Walk Test
Stair Climbing

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

Berger, K. I., Burton, B. K., Lewis, G. D., Tarnopolsky, M., Harmatz, P. R., Mitchell, J. J., ... Shaywitz, A. J. (2018). 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. In JIMD Reports (pp. 9-17). (JIMD Reports; Vol. 42). Springer. https://doi.org/10.1007/8904_2017_70
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. / 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. JIMD Reports. Springer, 2018. pp. 9-17 (JIMD Reports).
@inbook{2f853e6c5d9e45d1a34b26780ea953b1,
title = "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",
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.",
keywords = "Cardiopulmonary exercise test, Elosulfase alfa, Endurance, Enzyme replacement therapy, Exercise capacity, Mucopolysaccharidosis IVA",
author = "Berger, {Kenneth I.} and Burton, {Barbara K} and Lewis, {Gregory D.} and Mark Tarnopolsky and Harmatz, {Paul R.} and Mitchell, {John J.} and Nicole Muschol and Jones, {Simon A.} and Sutton, {V. Reid} and Pastores, {Gregory M.} and Heather Lau and Rebecca Sparkes and Shaywitz, {Adam J.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/8904_2017_70",
language = "English (US)",
series = "JIMD Reports",
publisher = "Springer",
pages = "9--17",
booktitle = "JIMD Reports",

}

Berger, KI, Burton, BK, Lewis, GD, Tarnopolsky, M, Harmatz, PR, Mitchell, JJ, Muschol, N, Jones, SA, Sutton, VR, Pastores, GM, Lau, H, Sparkes, R & Shaywitz, AJ 2018, 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. in JIMD Reports. JIMD Reports, vol. 42, Springer, pp. 9-17. https://doi.org/10.1007/8904_2017_70

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 proceedingChapter

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 -