MiToS and King's staging as clinical outcome measures in ALS: a retrospective analysis of the FORTITUDE-ALS trial.

Objective: To evaluate the Milano-Torino staging (MiToS) and King's staging systems as potential outcome measures for clinical trials in amyotrophic lateral sclerosis (ALS) by assessing these outcomes in FORTITUDE-ALS.

Methods: This was a analysis of the phase 2b FORTITUDE-ALS trial (NCT03160898), a double-blind, randomized, dose-ranging, placebo-controlled, parallel-group study of in patients with ALS. The treatment period was 12 weeks, with a follow-up assessment at week 16. Patients were retrospectively classified into MiToS and King's stages. Outcomes were the mean time maintaining baseline stage and risk of progression from the baseline stage to a later stage.

Results: The full analysis set consisted of 456 patients randomized 3:1 ( = 342, placebo  = 114) who received at least one dose of double-blind study drug and had at least one post-baseline assessment. At baseline, MiToS and King's stages were balanced between the and placebo groups: >99% of patients were in MiToS stage 0 or 1 and King's stage 1, 2 or 3. Time of maintaining the baseline stage was similar in both groups, for each staging system. The two staging systems exhibited considerably disparate results for risk of progression from baseline to a later stage: hazard ratio (HR) = 0.62 (95% confidence interval [CI] 0.38, 0.99) for MiToS and HR = 0.96 (95% CI 0.63, 1.44) for King's.

Conclusion: This exploratory analysis showed the feasibility of MiToS and King's staging as potential outcome measures in ALS. Additional studies of these staging systems are needed to further explore their utility in ALS clinical trials.