Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS.

摘要

To the Editor: We read with interest the article by Kfrnura et al.1 describing assessment of progression rate at time of diagnosis using the ALS Functional Rating Scale (ALSFRS-R). It is difficult to measure progression in amyotrophie lateral sclerosis (ALS) trials because there are no biomarkers, and the standard outcomes are clinical.Six months are needed to detect changes in the ALSFRS-R because of variability, due principally to differing rates of progression among patients. Stratified enrollment lowers variability by reducing heterogeneity in the treatment arms. While site of onset and riluzole treatment may impart modest effects, the person's rate of progression is the most important predictor of outcome. It is theoretically possible to assign strata using historical information on progression at the baseline visit of a trial using the DeltaFS.We measured the DeltaFS for our clinic patients to find the cutoff value that best dichotomizes the population into two groups for an upcoming phase II trial. We used DeltaFS = (48 - baseline ALSFRS-R)/time from onset to baseline (months). We took first visit to clinic as baseline. Unlike Kimura et al., who considered survival as primary endpoint, our primary outcome is the 6-month change in ALSFRS-R. Of 442 patients with information on DeltaFS (median = 0.55, interquartile range = [0.269, 1.11]), 112 patients had ASLFRS-R scores at baseline and 6 months later. The reduction in variance was maximized when the cutoff 0.50 per month was used to separate fast and slow progression: the mean of the 6-month score in the fast progression group was 4.11 points lower than that in the slow progression group (p < 0.0001). Using the cutoff suggested by Kimura et al. (0.67), variance reduction was significant (p = 0.0005) with mean for fast progression 3.67 lower than that for slow progression.