Prognostic factors for pulmonary milestones in Duchenne muscular dystrophy (DMD)



Poster Number: 115


Nathalie Goemans MD, PhD, James Signorovitch PhD, Gautam Sajeev ScD, Brenda Wong MD, Cuixia Tian MD, Craig McDonald MD, Eugenio Mercuri MD, PhD, Erik Niks MD, PhD, Zhiwen Yao BA, Association Française contre les Myopathies MPA, ImagingDMD Investigators BSc, PRO-DMD-01 Study Investigators MHS, Susan Ward PhD, Collaborative Trajectory Analysis Project


1. Neuromuscular Reference Center for Children, University Hospitals Leuven, 2. Analysis Group, Inc., 3. Analysis Group, Inc., 4. UMass Memorial Medical Center, 5. Cincinnati Children's Hospital Medical Center, 6. University of California Davis, 7. Universita Cattolica del Sacro Cuore, 8. Leiden University Medical Center, 9. Analysis Group, Inc., 10. Analysis Group, Inc., 11. Analysis Group, Inc., 12. Analysis Group, Inc., 13. Collaborative Trajectory Analysis Project

Knowledge of prognostic factors for pulmonary outcomes in DMD serves a general understanding of natural history and can help facilitate externally controlled studies and the long-term evaluation of novel therapies. We assessed prognostic factors for time to forced vital capacity (FVC) %-predicted < 80% (among n=368 boys free of this outcome at first assessment, 121 of whom eventually had the outcome) and time to FVC %-predicted < 50% (among n=488, 51 of whom eventually had the outcome) using Cox proportional hazards analyses. Data originated from three natural history databases (UZ Leuven, PRO-DMD-01 data provided by CureDuchenne, and Cincinnati Children's Hospital Medical Center) Average follow-up time was ~3 years. Being ambulatory at baseline and having higher baseline FVC %-predicted were significant predictors of longer time to pulmonary milestones. Prognostic accuracy was also compared between models based on age, data source, ambulatory status, and FVC %-predicted and models further incorporating steroid type, height, weight, BMI, and timed 10-meter walk/run velocity in ambulatory boys. The additional prognostic factors increased the pseudo-R2, a measure of the proportional of variability explained, from 0.20 to 0.31 for FVC %-predicted < 80% and from 0.16 to 0.19 for FVC %-predicted < 50%. Stratification of boys based on risk score tertiles produced groups with 2-year risks of reaching FVC %-predicted < 80% of 37%, 15%, and 4%, respectively; median times to FVC %-predicted < 80% in these groups were 2.4, 7.6 and 8.5 years, respectively. A prognostic score incorporating ambulatory status, level of 10MWR function for ambulatory boys, and baseline FVC%-predicted identified patients at significantly different levels of near-term risk of pulmonary decline.