Digital outcome captures longitudinal degradation of upper-limb function in non-ambulant patients affected by neuromuscular disorders

Precise upper limb function quantification is challenging but essential to judge efficacy of treatments for patients living with neuromuscular disorders. Lack of robust motor function endpoints has limited the number of clinical programs in this population and thus the access to innovative medication. The need for improving current outcomes and exploring innovative approaches, like wearable devices or video-based home assessment is consensual in the community. For ambulant patients affected by Duchenne muscular dystrophy (DMD), the EMA has recently qualified the first digital outcome as a primary endpoint in clinical trials: the stride velocity 95th percentile (SV95C). In this article we explore the possibility of using a similar outcome by measuring the motor function of the upper limbs in a population of non-ambulant patients affected with DMD and spinal muscular atrophy (SMA). Data for patients living with DMD was recorded in a natural history study including non-ambulant patients (N=16, age=13 ± 3 [8-19]). Comparison will be provided with data collected on non-ambulant patients affected by SMA. In both cases, patients wear two magneto-inertial measurement units, one on their wrist and one on their wheelchair. The digital outcome of interest quantifies the gestures where the patients develop the maximum energy with their upper limb, during the monthly recording period. It is called the 99th percentile of the total effort (TE99C). We compare the TE99C to the Performance of Upper Limb (PUL) scale in DMD and to the Motor Function Measurement (MFM32) in SMA. We evaluated the decrease of respectively PUL and MFM32 in the DMD and SMA studies and compared it to the evolution of TE99C. We will present the correlation between TE99C and the reference outcomes, as well as the longitudinal evolution of the different endpoints, in order to determine if the TE99C can constitute a valuable candidate to assess upper-limb motor function in neuromuscular disorders. Precise upper limb function quantification is challenging but essential to judge efficacy of treatments for patients living with neuromuscular disorders. Lack of robust motor function endpoints has limited the number of clinical programs in this population and thus the access to innovative medication. The need for improving current outcomes and exploring innovative approaches, like wearable devices or video-based home assessment is consensual in the community. For ambulant patients affected by Duchenne muscular dystrophy (DMD), the EMA has recently qualified the first digital outcome as a primary endpoint in clinical trials: the stride velocity 95th percentile (SV95C). In this article we explore the possibility of using a similar outcome by measuring the motor function of the upper limbs in a population of non-ambulant patients affected with DMD and spinal muscular atrophy (SMA). Data for patients living with DMD was recorded in a natural history study including non-ambulant patients (N=16, age=13 ± 3 [8-19]). Comparison will be provided with data collected on non-ambulant patients affected by SMA. In both cases, patients wear two magneto-inertial measurement units, one on their wrist and one on their wheelchair. The digital outcome of interest quantifies the gestures where the patients develop the maximum energy with their upper limb, during the monthly recording period. It is called the 99th percentile of the total effort (TE99C). We compare the TE99C to the Performance of Upper Limb (PUL) scale in DMD and to the Motor Function Measurement (MFM32) in SMA. We evaluated the decrease of respectively PUL and MFM32 in the DMD and SMA studies and compared it to the evolution of TE99C. We will present the correlation between TE99C and the reference outcomes, as well as the longitudinal evolution of the different endpoints, in order to determine if the TE99C can constitute a valuable candidate to assess upper-limb motor function in neuromuscular disorders.