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Brooks BR, Pioro EP, Katz J, et al. Slowing the loss of physical function in amyotrophic lateral sclerosis with edaravone: Post hoc analysis of ALSFRS-R item scores in pivotal study MCI186-19. Muscle Nerve. 2021;65(2):180-186doi: 10.1002/mus.27467.
Brooks, B. R., Pioro, E. P., Katz, J., Takahashi, F., Takei, K., Zhang, J., & Apple, S. (2022). Slowing the loss of physical function in amyotrophic lateral sclerosis with edaravone: Post hoc analysis of ALSFRS-R item scores in pivotal study MCI186-19. Muscle & nerve, 65(2), 180-186. https://doi.org/10.1002/mus.27467
Brooks, Benjamin Rix, et al. "Slowing the loss of physical function in amyotrophic lateral sclerosis with edaravone: Post hoc analysis of ALSFRS-R item scores in pivotal study MCI186-19." Muscle & nerve vol. 65,2 (2022): 180-186. doi: https://doi.org/10.1002/mus.27467
Brooks BR, Pioro EP, Katz J, Takahashi F, Takei K, Zhang J, Apple S. Slowing the loss of physical function in amyotrophic lateral sclerosis with edaravone: Post hoc analysis of ALSFRS-R item scores in pivotal study MCI186-19. Muscle Nerve. 2022 Feb;65(2):180-186. doi: 10.1002/mus.27467. Epub 2021 Dec 10. PMID: 34816454.
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Muscle Nerve. 2022 Feb;65(2):180-186. doi: 10.1002/mus.27467. Epub 2021 Dec 10.

Slowing the loss of physical function in amyotrophic lateral sclerosis with edaravone: Post hoc analysis of ALSFRS-R item scores in pivotal study MCI186-19.

Muscle & nerve

Benjamin Rix Brooks, Erik P Pioro, Jonathan Katz, Fumihiro Takahashi, Koji Takei, Jeffrey Zhang, Stephen Apple

Affiliations

  1. Atrium Health Neurosciences Institute, Carolinas Medical Center, University of North Carolina School of Medicine - Charlotte Campus, North Carolina, USA.
  2. Neuromuscular Division, Davee Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.
  3. Department of Neurology, Forbes Norris MDA/ALS Center, California Pacific Medical Center, San Francisco, California, USA.
  4. Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
  5. Princeton Pharmatech, Princeton, New Jersey, USA.
  6. Mitsubishi Tanabe Pharma America, Inc, Jersey City, New Jersey, USA.

PMID: 34816454 DOI: 10.1002/mus.27467

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.

© 2021 Mitsubishi Tanabe Pharma America, Inc. Muscle & Nerve published by Wiley Periodicals LLC.

Keywords: ALSFRS-R item scores; clinical trials; disease progression; functional decline; gross motor function

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