Predictability of disease progression in amyotrophic lateral sclerosis

Abstract

The aim of this study was to determine the predictors of disease progression in a group of 832 patients with the diagnosis of definite or probable amyotrophic lateral sclerosis (ALS). Disease progression was defined as the time to 20-point change in Appel ALS (AALS) score. The effects of individual prognostic factors on disease progression were assessed with the Kaplan-Meier life-table method. In addition, the prognostic value of each factor was estimated using both univariate and multivariate Cox proportional hazard analyses. The median time to a 20-point change in AALS score in our patient population was 9 months. Age, site of symptom onset, time between first symptom and first examination, total AALS score at first examination, and AALS preslope (rate of disease progression between first symptom and first examination) were significant and independent covariates of disease progression in our population. Identification of predictors of disease progression will facilitate better design of therapeutic trials, permitting the use of disease progression as a primary endpoint and improving baseline stratification of patient populations.

Prognosis and epidemiology of amyotrophic lateral sclerosis

“…[1][2][3][4][5][6][7]12,13,16 While we observed a 2.2-month decrease in median survival for those with bulbar disease compared to spinal onset patients, the average age of those diagnosed with a bulbar form of ALS was also notably higher in our patient population, easily accounting for the shorter survival in this group.…”

“…While many studies report that bulbar symptoms predict shorter survival, [1][2][3][4][5][6][7]13,14,18 in this study the univariate finding of shorter survival in patients with bulbar symptoms disappeared when multivariable analyses were applied (table 2). [1][2][3][4][5][6][7]12,13,16 While we observed a 2.2-month decrease in median survival for those with bulbar disease compared to spinal onset patients, the average age of those diagnosed with a bulbar form of ALS was also notably higher in our patient population, easily accounting for the shorter survival in this group.…”

“…It is unclear which, if any, of the clinical variables are important for predicting survival. Previous studies of ALS populations identified several negative prognostic factors, [1][2][3][4][5][6][7][8][9][10][11][12][13] including older age at onset, female sex, and bulbar onset. As there is so much inconsistency in the published literature regarding the relative importance of prognostic factors, clinicians are challenged to provide a well-reasoned prognosis to newly diagnosed patients.…”

Crowdsourced analysis of clinical trial data to predict amyotrophic lateral sclerosis progression

“…Overall, 15 different features were identified by more than one solver. Several were features reported in the literature 17,18,[24][25][26][27][28][29][30][31][32][33] , including age, site of disease onset, gender, the slope of disease progression so far, past ALSFRS slope, and past FVC slope, thus serving as validation of both the features and the algorithms. Unfortunately for many of the patients in PRO-ACT, FVC information was not available or other key features required to calculate FVC were missing.…”

Being PRO-ACTive: What can a Clinical Trial Database Reveal About ALS?

“…Using the PRO-ACT database allowed for validation of these findings; for example, site of onset has been shown to affect the slope of ALSFRS and overall survival time [33][34][35][36][37][38][39][40][41], with bulbar onset leading to poor prognosis compared with limb onset. Similarly, age of onset was predictive of prognosis (with poorer prognosis for patients with an later disease onset [34][35][36][37][38][39][40][41][42][43][44]). Other factors connected to prognosis in previous reports included body mass index or absolute weight [42,45]; cognitive functioning [46]; level of uric acid [42,47]; and levels of albumin and creatinine [48,49].…”