King's college progression rate at first clinical evaluation: A new measure of disease progression in amyotrophic lateral sclerosis

Background: To estimate King's college clinical stage progression rate (ΔKC) at first clinical evaluation in order to define its predictive and prognostic role on survival in a large cohort of Amyotrophic Lateral Sclerosis (ALS) patients. Methods: The ΔKC was calculated with the following formula: 0 - KC clinical stage at first clinical evaluation/disease duration from onset to first evaluation, and each result was reported as absolute value. All the evaluations were performed in two cohorts: one from our tertiary centre for motor neuron disease and the other one from a pooled resource open-access ALS clinical trials (PRO-ACT) database. C-statistic was used to evaluate the model discrimination of survival at different time points (1-3 years). Cox proportional hazard model was used to identify factors associated with survival. Results: ΔKC predicted survival at three years in our centre and in the PRO-ACT cohort (C-statistic 0.83, 95% CI 0.8-0.86, p < 0.0001; 0.7, 95% CI 0.68-0.73, p < 0.0001, respectively). At multivariate analysis, ΔKC was independently associated with survival both in our cohort (HR 3.62 95% CI 2.71-4.83 p = 0.001) and in the PRO-ACT cohort (HR 2.75 95% CI 2.1-3.6 p = 0.001). Conclusions: Based on our results, ΔKC could be used as a novel measure of disease progression, hence as an accurate predictor of survival in ALS patients. Indeed, greater values of ΔKC were associated with a 3.5-fold higher risk to experience the event, confirming its robust prognostic value.