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Abstract
Study MCI186-19 investigated the safety and efficacy of edaravone in the treatment of ALS. The 24-week, double-blind period was followed by a 24-week, open-label, active extension period. Patients originally receiving edaravone continued edaravone (E-E group, n = 65), and patients originally receiving placebo switched to edaravone (P-E group, n = 58). Because no statistical tests had been prospectively planned in the open-label period, we performed post-hoc analyses to assist in the interpretation of efficacy data. A mixed model for repeated measures (MMRM) and the Combined Assessment of Function and Survival (CAFS) were assessed. Additionally, slopes of time-dependent change between baseline in cycle 1 and the end of cycle 6 (24 weeks double-blind) and between the end of cycle 6 and end of cycle 12 (24 weeks open-label) were calculated using a random coefficient model including all available data during each period.
At week 48, the MMRM analysis showed significantly less decline in ALS Functional Rating Scale-Revised (ALSFRS-R) total score in the E-E group than in the P-E group (least-squares mean change from baseline ± standard error, 4.17 ± 1.40, p = 0.0037), meaning that the differences in the ALSFRS-R total score during the 24-week double-blind period were maintained in patients receiving edaravone for an additional 24 weeks. The CAFS endpoint (p = 0.0089) supported this finding. The slope analysis during the double-blind period showed a significant difference between the treatment groups, while there was no significant difference between the groups during the active extension period. These analyses suggest a potential benefit of early and continued edaravone treatment over delayed edaravone treatment.
Acknowledgements
The authors take full responsibility for the content of and the decision to submit this manuscript but thank David E. Hartree, under contract with Mitsubishi Tanabe Pharma America, and Teresa A. Oblak of Covance Market Access Services Inc., for providing research support, coordination assistance, and editorial contributions.
Declaration of interest
KT and KT are employees of Mitsubishi Tanabe Pharma Development America (MTDA). FT is an employee of Mitsubishi Tanabe Pharma Corporation (MTPC). JP is an employee of MTDA and MTPC.
Funding information
The edaravone MCI-186 clinical trials were funded by Mitsubishi Tanabe Pharma Corporation. This and the other articles in the ALSFTD Supplement, Edaravone (MCI-186) in ALS (Amyotrophic Lateral Sclerosis), were funded by Mitsubishi Tanabe Pharma America, Inc.