A novel quantitative indicator for disease progression rate in amyotrophic lateral sclerosis

Yuko Kobayakawa; Koji Todaka; Yu Hashimoto; Senri Ko; Wataru Shiraishi; Junji Kishimoto; Jun-Ichi Kira; Ryo Yamasaki; Noriko Isobe; Pooled Resource Open-Access ALS Clinical Trials Consortium

doi:10.1016/j.jns.2022.120389

A novel quantitative indicator for disease progression rate in amyotrophic lateral sclerosis

J Neurol Sci. 2022 Nov 15:442:120389. doi: 10.1016/j.jns.2022.120389. Epub 2022 Aug 24.

Authors

Yuko Kobayakawa¹, Koji Todaka², Yu Hashimoto³, Senri Ko³, Wataru Shiraishi³, Junji Kishimoto², Jun-Ichi Kira⁴, Ryo Yamasaki³, Noriko Isobe⁵; Pooled Resource Open-Access ALS Clinical Trials Consortium

Affiliations

¹ Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka 812-8582, Japan.
² Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka 812-8582, Japan.
³ Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
⁴ Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Translational Neuroscience Center, Graduate School of Medicine, School of Pharmacy at Fukuoka, International University of Health and Welfare, Okawa, Fukuoka 831-8501, Japan; Department of Neurology, Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Fukuoka 810-0022, Japan.
⁵ Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: isobe.noriko.342@m.kyushu-u.ac.jp.

PMID: 36041329
DOI: 10.1016/j.jns.2022.120389

Abstract

Objective: The current study sought to develop a new indicator for disease progression rate in amyotrophic lateral sclerosis (ALS).

Methods: We used a nonparametric method to score diverse patterns of decline in the percentage of predicted forced vital capacity (%FVC) in patients with ALS. This involved 6317 longitudinal %FVC data sets from 920 patients in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database volunteered by PRO-ACT Consortium members. To assess the utility of the derived scores as a disease indicator, we examined changes over time, the association with prognosis, and correlation with the Risk Profile of the Treatment Research Initiative to Cure ALS (TRICALS). Our local cohort (n = 92) was used for external validation.

Results: We derived scores ranging from 35 to 106 points to construct the FVC Decline Pattern scale (FVC-DiP). Individuals' FVC-DiP scores were determined from a single measurement of %FVC and disease duration at assessment. Although the %FVC declined over the disease course (p < 0.0001), the FVC-DiP remained relatively stable. Low FVC-DiP scores were associated with rapid disease progression. Using our cohort, we demonstrated an association between FVC-DiP and the survival prognosis, the stability of the FVC-DiP per individual, and a correlation between FVC-DiP scores and the TRICALS Risk Profile (r² = 0.904, p < 0.0001).

Conclusions: FVC-DiP scores reflected patterns of declining %FVC over the natural course of ALS and indicated the disease progression rate. The FVC-DiP may enable easy assessment of disease progression patterns and could be used for assessing treatment efficacy.

Keywords: Amyotrophic lateral sclerosis; Disease indicator; Disease progression rate; Forced vital capacity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyotrophic Lateral Sclerosis* / complications
Cohort Studies
Disease Progression
Humans
Prognosis
Vital Capacity