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J Neurol. 2019 Sep;266(9):2312-2321. doi: 10.1007/s00415-019-09401-1. Epub 2019 Jun 11.

Forced vital capacity and cross-domain late-onset Pompe disease outcomes: an individual patient-level data meta-analysis.

Author information

1
André Cournand Pulmonary Physiology Laboratory, Bellevue Hospital, New York, NY, USA. Kenneth.Berger@nyumc.org.
2
Division of Pulmonary, Critical Care and Sleep Medicine, New York University, New York, NY, USA. Kenneth.Berger@nyumc.org.
3
Precision Xtract, Vancouver, BC, Canada.
4
Precision Xtract, Oakland, CA, USA.
5
Sanofi Genzyme, Cambridge, MA, USA.

Abstract

BACKGROUND:

Late-onset Pompe disease (LOPD) is a rare, metabolic disease primarily affecting the musculoskeletal and respiratory systems. Forced vital capacity (FVC) is commonly used to measure pulmonary function; however, associations between FVC and other LOPD outcomes remain unclear.

METHODS:

A systematic literature review was conducted on November 2015, updated September 2016 and supplemented with clinical trial data from the sponsor. Outcomes included: 6-min walk test distance (6MWT), FVC, maximal inspiratory/expiratory pressure (MIP/MEP), Medical Research Council-skeletal muscle strength score (MRC), 36-item short-form survey-physical component score (SF-36), Rotterdam Handicap Scale (RHS), Fatigue Severity Scale (FSS) and survival. Individual patient data meta-analysis was used for cross-sectional analyses and longitudinal analyses to determine associations between percent of predicted FVC and LOPD measures and outcomes.

RESULTS:

Fifteen studies were selected. From cross-sectional analyses, FVC and MRC were most strongly associated. Specifically, patients with 10% higher FVC (a round number for illustrative purposes only) were associated with a 4.72% (95% confidence interval [CI]: 3.37, 6.07) higher MRC score, indicating a positive association. Similarly, slopes for the 6MWT and SF-36 relative to a 10% higher FVC were estimated at 33.2 meters (95% CI 24.0, 42.4) and 1.2% (95% CI 0.24, 2.16%), respectively. From longitudinal analyses, a 10% incremental increase in predicted FVC was associated with an average increase of 4.12% in MRC score (95% CI 1.29, 6.95), 35.6 m in the 6MWT (95% CI 19.9, 51.6), and 1.34% in SF-36 (95% CI 0.08, 2.60). There was insufficient data to conduct analyses for RHS, FSS and survival.

CONCLUSIONS:

FVC is positively associated with LOPD measures and outcomes across multiple domains. Additionally, longitudinal changes in FVC are positively associated with changes in the 6MWT, MRC and SF-36.

KEYWORDS:

6-min walk test; Forced vital capacity; Individual patient-level data meta-analysis; Late-onset Pompe disease

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