Analysis of patient reported outcomes from the CINRG Becker Natural History Study

Topic:

Clinical Trials

Poster Number: 70

Author(s):

Utkarsh Dang, PhD, Carleton University, Khalil Kain, Carleton University, Alaina Giacobbe, University of Pittsburgh School of Medicine, Heather Gordish-Dressman, PhD, Children’s National Hospital, Gabriela Niizawa, CCRP, University of Pittsburgh, Ksenija Gorni, MD PhD, Roche, Michela Guglieri, MD, Newcastle University, Anne Connolly, MD, Nationwidechildren's Hospital, Matthew Wicklund, MD, University of Colorado School of Medicine, Tulio Bertorini, MD, University of Tennessee Health Science Center, Jean Mah, MD, Alberta Children’s Hospital Research Institute, Mathula Thangarajh, MD, PhD, Children’s National Medical Center, Edward Smith, MD, Duke University School of Medicine, Nancy Kuntz, MD, Northwestern University Feinberg School of Medicine, Craig McDonald, MD, University of California Davis Health, Erik Henricson, PhD MPH, University of California at Davis, Saila Upadhyayula, MD, Emory University School of Medicine, Barry Byrne, MD, PhD, University of Florida, Georgios Manousakis, MD, University of Minnesota Medical School, Amy Harper, MD, VCU School of Medicine, Susan Iannaccone, MD, UTSW, Paula Clemens, MD, University of Pittsburgh

Background: Becker muscular dystrophy (BMD) has a broad phenotype with progressive muscle weakness and cardiomyopathy that can occur either early in life or decades later. From the perspective of future treatment trial design and clinical care, understanding the natural history of BMD, especially through the lens of patient reported outcomes (PROs), is needed.
Objective: To characterize quality of life (QOL) via PROs.
Approach: We conducted the Becker Natural History Study (BNHS), a prospective, natural history study of males with BMD and obtained NeuroQOL and PedsQL questionnaire responses, as well as clinical outcomes on 76 participants (9 to 75 years of age). Analyses were stratified by age (<18 or ≥18 years old). QOL questionnaires were from five subdomains: anxiety, depression, and fatigue, and upper and lower extremity function. We conducted binned repeated cross-sectional analyses, longitudinal analyses, and correlations of PRO and clinical outcomes. Results: The median score for anxiety, depression, and fatigue subdomains was worse for adults than for minors. Larger floor and ceiling effects were seen for depression (higher=worse) and extremity functions (higher=better), respectively, for the minors compared to adults. After stratification, a clear trend was only seen for lower extremity function at baseline. Upper and lower extremity scores (r=0.73), as well as pairs of depression, anxiety, and fatigue were more strongly associated than pairwise relationships between motor and mental/social subdomains. Lower extremity scores had stronger correlations with motor outcomes as compared to upper extremity scores (which remained more stable across 3 year follow-up). Across visits, no clear trend was seen in adults for anxiety or depression. Conclusions: PROs provided insight into BMD progression in adults. Individual questions provided insight into most extremely-rated responses. Correlations between subdomain scores suggest that disease progression may not be the sole influencer on QOL. While the sample size was small, our data characterized QOL outcomes in a prospective cohort.