Abstract
Introduction: Phase 3 study MCI186-19 demonstrated less loss of physical function with edaravone versus placebo, as measured by the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score. A 1-point drop in an individual ALSFRS-R item may be clinically meaningful. We assessed ALSFRS-R item score changes to identify clinical features protected by edaravone treatment. Methods: Time-to-event analysis was used to assess the cumulative probabilities of reductions in ALSFRS-R item scores and Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) subdomain scores. Results: Edaravone use was accompanied by: (1) delayed drop of ≥1 point in ALSFRS-R item score for four items: salivation, walking, climbing stairs, orthopnea (unadjusted), or for two items: walking, climbing stairs (after Bonferroni correction for multiple comparisons); (2) delayed score transition from 4 or 3 at baseline to ≤2 for five items: swallowing, eating motion, walking, climbing stairs, orthopnea (unadjusted), or for one item: climbing stairs (after Bonferroni correction for multiple comparisons); and (3) delayed worsening of ALSAQ-40 domain scores representing daily living/independence, eating and drinking (unadjusted). Discussion: These post-hoc analyses identified the ALSFRS-R item scores and ALSAQ-40 domain scores that were associated with preserved gross motor function and health-related quality of life, respectively, after edaravone treatment. Limitations of post-hoc analyses should be considered when interpreting these results. We recommend that clinical trials employing the ALSFRS-R include this type of analysis as a pre-specified secondary outcome measure.
Original language | English (US) |
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Pages (from-to) | 180-186 |
Number of pages | 7 |
Journal | Muscle and Nerve |
Volume | 65 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2022 |
Funding
We thank Endou Mai of Mitsubishi Tanabe Pharma Corporation (MTPC), Inc., for assistance with statistical analyses. ‐value communications provided support for technical writing, editing, and publication assistance and was funded by Mitsubishi Tanabe Pharma America, Inc. (MTPA). Study 19 was funded by MTPC, and this post hoc analysis was funded by MTPA. MTPA and MTPC did not have any input into the manuscript beyond the input provided by the authors. p
ASJC Scopus subject areas
- Clinical Neurology
- Physiology (medical)
- Cellular and Molecular Neuroscience
- Physiology