Labra J, Menon P, Vucic S. Rate of Disease Progression: A Prognostic Biomarker in ALS. J Neurol Neurosurg Psychiatry 2016;87:628–632.
Submitted by David Haustein, MD, News Science Editorial Board
The ALSFRS-R is a commonly used clinical biomarker to monitor function in patients with ALS but does not account for the rate of disease progression, which is an independent predictor of survival. A previous study of 82 patients with ALS in Japan investigated the rate of disease progression (ΔFS) at the initial visit as a biomarker using the following formula:
ΔFS = 48 – (Total ALSFRS-R at initial visit)
Symptom duration (months)
Higher numbers, therefore, indicate faster progression. Building upon this initial work, clinicians in this Australian study recruited a cohort of 203 patients with possible, probable, or definite ALS between 2004 and 2014, of whom 164 met inclusion criteria. Using history obtained from the patient and family members, rate of disease progression was calculated. The primary end point was survival. Statistical analysis were used to define rate of progression cutoff values of <0.47 (slower progression), 0.47-1.11 (intermediate progression), and >1.11 (faster progression). Median survival time from the initial visit was 2.4 years for the slow progressing group, 1.6 years for the intermediate group, and 0.7 years for the fast progressing group. Age 70 years or greater, shorter duration of symptoms, lower total ALSFRS-R score, ALSFRS-R respiratory subscore <10, and bulbar onset disease at initial visit were associated with worse prognosis.
Comment: While the conclusion that a faster rate of progression at initial assessment of a patient with ALS portends a poorer prognosis is intuitive, this study provides more precise quantification of this phenomenon. Discriminant points were defined, and these could be employed in the clinic, and possibly to define groups of slow, intermediate, and fast progressing patients for clinical trial purposes. Caution must be used in applying these results, as substantial errors might be made in computing the denominator of ΔFS.
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