TY - JOUR
T1 - MiToS and King’s staging as clinical outcome measures in ALS
T2 - a retrospective analysis of the FORTITUDE-ALS trial
AU - Gebrehiwet, Paulos
AU - Meng, Lisa
AU - Rudnicki, Stacy A.
AU - Sarocco, Phil
AU - Wei, Jenny
AU - Wolff, Andrew A.
AU - Chiò, Adriano
AU - Andrews, Jinsy A.
AU - Genge, Angela
AU - Jackson, Carlayne E.
AU - Lechtzin, Noah
AU - Miller, Timothy M.
AU - Shefner, Jeremy M.
N1 - Funding Information:
FORTITUDE-ALS was conducted by Cytokinetics, Incorporated in collaboration with Astellas Pharma Inc. The authors acknowledge Jayna Patel, PhD (Evidence Scientific Solutions, Horsham, UK) and Richard Fay, PhD, CMPP (Evidence Scientific Solutions, Philadelphia, PA, US) for editorial assistance, which was funded by Cytokinetics, Incorporated. We wish to thank the participants of FORTITUDE-ALS and their families for their contributions to this clinical trial, the investigators of FORTITUDE-ALS, FORTITUDE-ALS study group and members of the Data Monitoring Committee and Steering Committee.
Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2023
Y1 - 2023
N2 - 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 post hoc analysis of the phase 2b FORTITUDE-ALS trial (NCT03160898), a double-blind, randomized, dose-ranging, placebo-controlled, parallel-group study of reldesemtiv 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 (reldesemtiv n = 342, placebo n = 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 reldesemtiv 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.
AB - 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 post hoc analysis of the phase 2b FORTITUDE-ALS trial (NCT03160898), a double-blind, randomized, dose-ranging, placebo-controlled, parallel-group study of reldesemtiv 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 (reldesemtiv n = 342, placebo n = 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 reldesemtiv 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.
KW - King’s staging
KW - MiToS
KW - Randomized clinical trial
KW - amyotrophic lateral sclerosis
KW - reldesemtiv
UR - http://www.scopus.com/inward/record.url?scp=85144102262&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85144102262&partnerID=8YFLogxK
U2 - 10.1080/21678421.2022.2154678
DO - 10.1080/21678421.2022.2154678
M3 - Article
C2 - 36503310
AN - SCOPUS:85144102262
SN - 2167-8421
VL - 24
SP - 304
EP - 310
JO - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
JF - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
IS - 3-4
ER -