TY - JOUR
T1 - Slowing the loss of physical function in amyotrophic lateral sclerosis with edaravone
T2 - Post hoc analysis of ALSFRS-R item scores in pivotal study MCI186-19
AU - Brooks, Benjamin Rix
AU - Pioro, Erik P.
AU - Katz, Jonathan
AU - Takahashi, Fumihiro
AU - Takei, Koji
AU - Zhang, Jeffrey
AU - Apple, Stephen
N1 - Funding Information:
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
Publisher Copyright:
© 2021 Mitsubishi Tanabe Pharma America, Inc. Muscle & Nerve published by Wiley Periodicals LLC.
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
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U2 - 10.1002/mus.27467
DO - 10.1002/mus.27467
M3 - Article
C2 - 34816454
AN - SCOPUS:85121401013
SN - 0148-639X
VL - 65
SP - 180
EP - 186
JO - Muscle and Nerve
JF - Muscle and Nerve
IS - 2
ER -