#apaperaday: Stride Velocity 95th Centile Detects Decline in Ambulatory Function Over Shorter Intervals than the 6-Minute Walk Test or North Star Ambulatory Assessment in Duchenne Muscular Dystrophy

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Stride Velocity 95th Centile Detects Decline in Ambulatory Function Over Shorter Intervals than the 6-Minute Walk Test or North Star Ambulatory Assessment in Duchenne Muscular Dystrophy

#apaperaday from @journal_nd by Rabbia et al on the ability of the stride velocity 95th centile (SV95C) to detect a decline in ambulatory function in a Duchenne trial for taldefgrobep (anti-myostatin antibody from BMS/Roche). DOI: 10.3233/JND-230188

Duchenne is characterized by progressive loss of muscle function. Trials are ongoing to test the efficacy of many treatments. However, the challenge is that treatments slow down progression in a slowly progressive disease. So you need very sensitive outcome measures.

Usually outcome measures are done in a hospital setting, e.g., 6 minute walk test and the North Star Ambulatory Assessment. This means a trial visit, which can be a burden to families and also is a snapshot of function at that moment – not per se representative for general status.

Authors here present a wearable as an alternative outcome. The wearable is worn at the ankle and measures velocity, acceleration and angular movement. The outcome measure distilled from this wearable is the SV95C, which is the 5% of fastest strides detected.

This outcome is EMA qualified for Duchenne patients 4 & older, provided a wearable can measure according to set specifics, e.g., actimyo. Normative data is available. Here authors present data from a clinical trial where the actimyo was used in a subset of patients.

This was the taldefgrobep study that was stopped early due to futility (no treatment effect was seen at an interim analysis so it was not ethical to continue the trial). Still, the data can be used to study the subgroup where the 95SVC was measured along with other outcomes.

This subgroup consisted of 52 patients, where for 47 there was useful data at baseline and at at least one post-baseline timepoint (i.e., 50 hours of measurement at each time point). The data showed that baseline groups were comparable also for SV95C (as with other outcomes).

The data also showed a good correlation between the SV95C and the 4 stair climb velocity, North Star Ambulatory Assessment, and 6-minute walk distance. All outcomes showed a decline from baseline – there was no difference between treatment and placebo groups (as was known).

Authors discuss for the SV95C there was relatively low variability between patients and there was consistency with other outcomes. The compliance was reasonable – about 10% of patients did not wear the actimyo for a sufficient time to capture 50 hours of data per timepoint.

Especially at later time points, they had less data. This was not per se due to lack of compliance but because the trial was terminated and therefore lower numbers had longer-term data. Authors expect that compliance will improve now SV95C is accepted by EMA as a primary endpoint.

Authors stress that they can measure a change with the SV95C and that it can measure meaningful declines in patients earlier than e.g., NSAA and 6MWT. However, for now this is based only on a small sample set and a single trial.

Note that authors could not test whether the SV95C could also mention a therapeutic response, as the trial tested a drug that turned out not to be effective. Measuring a meaningful decline in natural history is not the same as measuring a meaningful reduction of decline.

Authors outline SV95C can capture outcomes in the home environment. Levels depend on patient age & disease stage. More work is needed to elucidate results in different age groups, but also the impact of seasons and climate (valid point that I can relate to with 4 weeks of rain).

Authors outline this trial did not capture steroid type & regimen so they could not assess the impact of those variables on the SV95C data. So more work is needed as always, but I do appreciate that on top of ‘this treatment does not work’ more information came out of this trial.