title: Hip flexion weakness is associated with impaired mobility in oculopharyngeal muscular dystrophy: a retrospective study with implications for trial design.
abstract: Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy for which validated outcome measures are lacking, posing a barrier to clinical trials. Our goal was to identify factors associated with impaired mobility in OPMD in order to guide development of surrogate endpoints in future clinical trials. One hundred forty-four individuals with OPMD were included in this retrospective, single-center study. We made novel use of parametric time-to-event analysis to model age at initial use of assistive device for ambulation. We hypothesized that limb weakness and other markers of disease severity are associated with earlier use of assistive devices. 23.6% of individuals (34/144) progressed to use of assistive devices (mean age 66.0 ± 9.6 y). Earlier age at assistive device was associated with hip flexion Medical Research Council grade ≤3 (p <0.0001), earlier disease onset (p <0.0001), and lack of blepharoptosis surgery (p = 0.011). Markers of dysphagia severity were not associated with earlier progression to assistive devices. Our study is the first to show a statistical association between hip flexion weakness and impaired mobility in OPMD, indicating that hip flexion strength could be explored as a surrogate endpoint for use in clinical trials. Since severity of disease features may be discordant within individuals, composite outcome measures are warranted.
authors.affiliation: Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM, United States. Electronic address: syoussof@salud.unm.edu.
authors.forename: Sarah
authors.initials: S
authors.lastname: Youssof
authors.affiliation: Clinical and Translational Science Center, University of New Mexico Health Sciences Center, Albuquerque, NM, United States.
authors.forename: Ronald
authors.initials: R
authors.lastname: Schrader
authors.affiliation: Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, United States.
authors.forename: David
authors.initials: D
authors.lastname: Bear
authors.affiliation: Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM, United States.
authors.forename: Leslie
authors.initials: L
authors.lastname: Morrison
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001763:Blepharoptosis / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D015897:Comorbidity; D003680:Deglutition Disorders / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006615:Hip / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D039141:Muscular Dystrophy, Oculopharyngeal / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D009516:New Mexico / Q000453:epidemiology; D015995:Prevalence; D012189:Retrospective Studies; D012656:Self-Help Devices; D012720:Severity of Illness Index; D012782:Shoulder / Q000503:physiopathology
keywords: Mobility impairment; Natural history; Oculopharyngeal muscular dystrophy; Outcome measures; Time-to-event analysis