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 4 items: salivation, walking, climbing stairs, orthopnea (unadjusted), or for 2 items: walking, climbing stairs (after Bonferroni correction for multiple comparisons); [2] delayed score transition from 4 or 3 at baseline to ≤2 for 5 items: swallowing, eating motion, walking, climbing stairs, orthopnea (unadjusted), or for 1 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.