P.455 - Outcome measures for Duchenne muscular dystrophy from ambulant to non-ambulant patients: implications for clinical trials

Abstract

The need for a better understanding of Duchenne muscular dystrophy (DMD) natural history and the role of novel outcome measures and their impact in current and future clinical trials is well recognized. We aimed to assess the natural history of ambulant and non-ambulant DMD patients in an international multicentre study across 5 centres (London, Newcastle, Paris, Leiden, Nijmegen) with patients being assessed 6-monthly according to a shared protocol. Assessments included 6-minute walk distance (6MWD), North Star Ambulatory Assessment (NSAA), Performance of Upper Limb (PUL 1.2), MyoSet, respiratory function (forced vital capacity – FVC, maximum inspiratory and expiratory pressures – MEP and MIP, peak expiratory flow – PEF, peak cough flow – PCF). A subgroup performed annual whole body DEXA scans. We analysed longitudinal data for 82 patients (at recruitment 53 ambulant, mean age = 7.7 ± 2.3 years and 29 non-ambulant, mean age = 14.4 ± 1.9 years). For ambulant patients >7years old we observed a decline of 2.6 points per year in the NSAA (p < 0.001) and an increase of 1.04 seconds per year in the time to run 10 meters (p < 0.001). In non-ambulant patients, we observed a loss of 3.96 points on the PUL per year (p < 0.001) and a decrease in most of the %predicted respiratory measures (6.5% in FVC p < 0.001, 3.7% in PEF p < 0.01, 3.4% MIP p < 0.001 and 2.5% MEP p < 0.001) over the year. We observed a strong correlation between the PUL total and %predicted FVC (r = 0.73, p < 0.001) and between best MIP and moviplate (r = 0.71, p < 0.001). Patients with a lower limb lean body mass >30% were all ambulant except for 1 patient who lost ambulation less than 6 months later. This study adds to the current knowledge on DMD natural history. In particular, herein we explored the mean changes per year expected for non-ambulant patients for the different respiratory outcome measures and for functional measures that will be relevant for trials targeting this population. We also characterized the relationship between respiratory measures and upper limb function.