Hip flexion weakness is associated with impaired mobility in oculopharyngeal muscular dystrophy: a retrospective study with implications for trial design.
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.
['Youssof|Sarah|S|', 'Schrader|Ronald|R|', 'Bear|David|D|', 'Morrison|Leslie|L|']
D000328:Adult D000367:Age Factors D000368:Aged D000369:Aged, 80 and over D001763:Blepharoptosis D015897:Comorbidity D003680:Deglutition Disorders D018450:Disease Progression D005260:Female D006615:Hip D006801:Humans D008297:Male D008875:Middle Aged D018908:Muscle Weakness D039141:Muscular Dystrophy, Oculopharyngeal D009516:New Mexico D015995:Prevalence D012189:Retrospective Studies D012656:Self-Help Devices D012720:Severity of Illness Index D012782:Shoulder
Oculopharyngeal muscular dystrophy Outcome measures Time-to-event analysis Mobility impairment Natural history