{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:07:46Z","timestamp":1784268466512,"version":"3.55.0"},"reference-count":30,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"abstract":"<jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Respiratory impairment in neuromuscular disorders (NMDs) is generally assessed using forced vital capacity (FVC). Any improvement in FVC trajectory will delay ventilatory support; however, the change required for patients to perceive a noticeable clinical benefit, the clinically meaningful threshold (CMT), has not been defined in NMDs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>To derive the within-person and between-group CMTs for FVC (% predicted) in patients with late-onset Pompe disease (LOPD).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This analysis leverages data from the Phase 3 COMET trial (NCT02782741, registered 25 May 2016), which assessed the efficacy of avalglucosidase alfa (AVA) versus alglucosidase alfa (ALG) on upright FVC (% predicted) in LOPD. Anchor- and distribution-based methods were used to estimate the within-person and between-group CMTs for FVC at Weeks 49 and 97.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>COMET enrolled 99 participants aged \u226518 years (52% male; mean age 48.0 years). The within-person CMT for absolute change in FVC expressed as % predicted was estimated as 3.0% [95% confidence interval (CI) 2.3, 3.8]. The proportion of patients with a meaningful increase in FVC was higher in the AVA versus ALG group across the CI of the estimated CMT (odds ratios: 2.3\u20132.6; nominal p-values: 0.026\u20130.058). The between-group CMT, needed to evaluate differences between treatment groups, was estimated as 2.1% predicted [95% CI 1.1, 3.1].<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>\n              We identified a narrow range of within-person and between-group CMTs for upright FVC (% predicted) in LOPD.\n              <jats:italic>Post hoc<\/jats:italic>\n              application of these thresholds to COMET showed that a greater proportion of patients in the AVA group had clinically meaningful improvement in FVC versus ALG. These findings may aid in interpretation of data from studies in other NMDs.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1177\/22143602251332829","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T14:42:51Z","timestamp":1747838571000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Defining clinically meaningful thresholds for forced vital capacity in patients with neuromuscular disorders: Lessons learned from the COMET study in Pompe disease"],"prefix":"10.1177","author":[{"given":"Kenneth I","family":"Berger","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, NYU Grossman School of Medicine, and the Andr\u00e9 Cournand Pulmonary Physiology Laboratory, Bellevue Hospital, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ivanescu","sequence":"additional","affiliation":[{"name":"IQVIA, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Msihid","sequence":"additional","affiliation":[{"name":"Sanofi, Gentilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Periquet","sequence":"additional","affiliation":[{"name":"Sanofi, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Hamed","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina an","family":"Haack","sequence":"additional","affiliation":[{"name":"Sanofi, Gentilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyue","family":"Zhou","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"van der Beek","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center, Rotterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Boentert","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University of M\u00fcnster, M\u00fcnster, Germany"},{"name":"Department of Medicine, UKM-Marienhospital Steinfurt, Steinfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Pulikottil-Jacob","sequence":"additional","affiliation":[{"name":"Sanofi, Reading, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Pollissard","sequence":"additional","affiliation":[{"name":"Sanofi, Gentilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00794"},{"key":"e_1_3_3_3_2","first-page":"111","article-title":"Respiratory management of patients with neuromuscular disease: current perspectives","volume":"6","author":"Pfeffer G","year":"2016","unstructured":"Pfeffer G, Povitz M. 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