Article Text
Abstract
Background The Gold Coast criteria (GCC) have been proposed as a means of selecting patients for amyotrophic lateral sclerosis (ALS) clinical trials. We aimed to characterise disease progression according to the GCC.
Methods Data from population-based ALS registries from the Netherlands and Belgium were analysed. The GCC additionally define ALS as lower motor neuron (LMN) dysfunction in ≥2 body regions without upper motor neuron dysfunction. Therefore, the revised El Escorial criteria (rEEC) were supplemented with a ‘Gold Coast ALS’ category for patients with only LMN dysfunction in ≥2 body regions. We assessed survival time, ALS Functional Rating Scale (ALSFRS-R) progression rates and between-patient variability per diagnostic category.
Results We included 5957 ALS patients, of whom 600 (10.1%) fulfilled the GCC but not the rEEC, and 95 (1.6%) fulfilled only the rEEC. ALSFRS-R progression rates were similar for the rEEC (0.84 points/month) and GCC (0.81 points/month) with similar variability (standard deviation of 0.59 vs. 0.60) and median survival time (17.8 vs.18.7 months). Survival time and average progression rates varied (p<0.001) between categories. Per category, however, there was considerable between-patient variability with progression rates ranging from: −2.10 to −0.14 (definite), −1.94 to −0.06 (probable), −2.10 to −0.02 (probable laboratory supported), −1.79 to −0.02 (possible) and −1.31 to 0.08 (Gold Coast).
Conclusions The GCC broaden the definition of ALS, allowing more patients to participate in trials, while minimally impacting population heterogeneity. Given the large variability per diagnostic category, selecting only specific categories for trials may not result in a more homogeneous study population.
- ALS
- NEUROMUSCULAR
- MOTOR NEURON DISEASE
Data availability statement
Data are available on reasonable request. All protocols, analyses and anonymised data will be shared on request from any qualified investigator.
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Data availability statement
Data are available on reasonable request. All protocols, analyses and anonymised data will be shared on request from any qualified investigator.
Footnotes
LHvdB and RPAvE contributed equally.
Contributors ADdJ, NB, MW, PvD, LHvdB and RPAvE contributed to the conception and design of the study. ADdJ, MAvE, PM, JHV, PvD, LHvdB and RPAvE contributed to the acquisition of the data. ADdJ and RPAvE analysed the data, drafted the figures and the manuscript. All authors revised the manuscript for intellectual content.
Funding This study was funded by Netherlands ALS Foundation.
Competing interests ADdJ, MW, NB, MAvE, PM, JHV, LHvdB and RPAvE report no disclosures relevant to this study. PvD holds a senior clinical investigatorship of FWO-Vlaanderen and is supported by the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders, the ALS Liga België and the KU Leuven funds 'Een Hart voor ALS', 'Laeversfonds voor ALS Onderzoek' and the 'Valéry Perrier Race against ALS Fund'. Several authors of this publication are member of the European Reference Network for Rare Neuromuscular Diseases (ERN-NMD).
Provenance and peer review Not commissioned; externally peer reviewed.
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