MiToS and King\u27s 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\u27s 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 RESULTS: The full analysis set consisted of 456 patients randomized 3:1 ( CONCLUSION: This exploratory analysis showed the feasibility of MiToS and King\u27s staging as potential outcome measures in ALS. Additional studies of these staging systems are needed to further explore their utility in ALS clinical trials

Feasibility assessment of using the MiToS staging system for conducting economic evaluation in amyotrophic lateral sclerosis

This study assessed the feasibility of using the Milano-Torino staging (MiToS) system for conducting economic evaluation to measure health outcomes in amyotrophic lateral sclerosis (ALS). A Markov model was developed using the MiToS system and evaluated with a hypothetical treatment versus standard of care. Health utilities and transition probabilities were derived from the literature. Four-time horizons (1, 5, 10, and 20 years) were examined. Treatment effects of 20–35% relative risk reduction (RRR) of progressing to the next MiToS stage were assessed. Three patient distribution scenarios were tested: (1) all patients began in stage 0; (2) patient distribution based on real-world TONiC study; (3) distribution based on the PRO-ACT database. Health outcomes (quality-adjusted life-years [QALYs], life-years [LYs]) were reported with a 3% discount rate. A time horizon of 10 years fully captured treatment benefits: incremental QALYs were 0.28–0.60, 0.21–0.45, and 0.26–0.55 for scenarios 1–3, respectively; incremental LYs were 0.56–1.17, 0.46–0.97, and 0.53–1.11, respectively. MiToS-based staging can be used for conducting economic analyses in ALS. Estimated incremental QALY and LY gains were meaningful within the context of ALS, for hypothetical treatments with RRR of 20–35%.</p

Health utilities and quality-adjusted life years for patients with amyotrophic lateral sclerosis receiving <i>reldesemtiv</i> or placebo in FORTITUDE-ALS.

AimsTo estimate the health utilities and quality-adjusted life years (QALYs) in patients with amyotrophic lateral sclerosis (ALS) receiving reldesemtiv versus placebo in FORTITUDE-ALS.Materials and methodsWe performed a post hoc analysis of clinical trial data from FORTITUDE-ALS (NCT03160898). This Phase IIb, double-blind, randomized, dose-ranging, placebo-controlled, parallel-group, 12-week trial evaluated reldesemtiv in patients with ALS. Health utilities from the five-level version of the EuroQol five-dimensional questionnaire (EQ-5D-5L) were estimated using ALS Functional Rating Scale-Revised (ALSFRS-R) scores collected during the trial. QALYs were estimated using the area under the curve method.ResultsThe full analysis set consisted of 456 patients (reldesemtiv n = 342, placebo n = 114), who received at least one dose of the double-blind study drug, and had ALSFRS-R assessed at baseline and at least one post-baseline assessment. The difference in EQ-5D-5L utility least-squares (LS) mean change from baseline to week 12 for reldesemtiv versus placebo, adjusted for baseline values, was statistically significant (0.03, 95% confidence interval [CI]: 0.01, 0.05; p = .0008). The incremental QALY of reldesemtiv versus placebo adjusted for baseline utility values showed a modest, but statistically significant, difference (0.004, 95% CI: 0.001, 0.007; p = .0058).ConclusionsThis post hoc analysis of FORTITUDE-ALS suggests that reldesemtiv showed a modest but significant benefit in health utilities and QALYs compared with placebo. Future long-term studies that include direct collection of EQ-5D-5L data will be needed to confirm our findings.Clinicaltrials.gov identifierNCT03160898