ALSFRS-R decline rate prior to baseline is not useful for stratifying subsequent progression of functional decline

Abstract

Objective

One of the difficulties in developing a novel drug for patients with amyotrophic lateral sclerosis (ALS) is the significant variation in the clinical course. To control this variation, a 12-week run-in period is used in some clinical trials. Based on the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) change during the run-in period, only moderate progressors are selected in some clinical trials. Some reports showed that the ALSFRS-R progression rate was associated with survival. However, it is unclear whether the ALSFRS-R change in the run-in period is a useful prognostic factor of the ALSFRS-R change from baseline. In addition, we explore the inclusion criteria that could control the variability in ALS-function progression without setting a run-in period.

Methods

We utilized the Japanese and US ALS registry databases (JaCALS and PRO-ACT). Patients were classified into three populations (rapid, moderate, and slow progressors) based on the ALSFRS-R change prior to baseline. We also classified patients into three prognostic populations based on the ALSFRS-R change from baseline. We confirmed whether each of the three populations were matched with their respective three prognostic populations.

Results

Our data showed that the three groups classified by the ALSFRS-R change during the 12 weeks prior to baseline or by the rate of progression from onset to baseline did not accord with the three prognostic groups.

Conclusions

Our results showed that the ALSFRS-R change in the run-in period or from onset to baseline is not useful for stratifying subsequent progression of functional decline in clinical trials.

Keywords:

• JaCALS
• PRO-ACT, ALSFRS-R, clinical trial
• heterogeneity

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Correction

Correction Statement

This article was originally published with errors, which have now been corrected in the online version. Please see Correction (http://dx.doi.org/10.1080/21678421.2024.2320987).

Acknowledgements

We would like to thank the doctors and staff as well as all the patients with ALS who participated in JaCALS and PRO-ACT. We would also like to extend our thanks to Ariko Takanashi, Shinichi Kanazawa, Yoshinori Imokawa and Takahiro Higuchi from A2 Healthcare Corporation who supported the analysis of the data from JaCALS.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

PRO-ACT data are openly available at https://ncri1.partners.org/ProACT. The participants of JaCALS did not give written consent for their data to be shared publicly, so due to the sensitive nature of the research supporting data is not available.

Additional information

Funding

Tatsuto Hamatani and Fumiya Sano are employees of Sumitomo Pharma Co., Ltd. This study was supported by Sumitomo Pharma Co., Ltd. The other authors report that they have no competing interests to declare.