Characterizing patients with amyotrophic lateral sclerosis (ALS) according to the Gold Coast criteria (GCC) may allow for more patients to participate in clinical trials, however, it does not necessarily result in a more homogeneous study population. These were the findings of a study published in Journal of Neurology, Neurosurgery, & Psychiatry.
Patients with ALS present with heterogeneous symptoms, complicating the process of drug development. Most clinical trials for ALS use the revised El Escorial criteria (rEEC) to stratify and recruit patients. In this study, categorizing patients with the GCC was evaluated for potential use in clinical trial recruitment.
Data for this study were sourced from 2 prospective population-based registries in the Netherlands and Belgium collected between 2006 and 2020. Patients were evaluated by the rEEC and GCC and categorized as Definite ALS, Probable ALS, Probable ALS laborator-supported, Possible ALS, Gold Coast ALS, and not Gold Coast ALS. Gold Coast ALS was defined as the absence of upper motor neuron dysfunction with progressive lower motor dysfunction in 2 or more body regions. Not Gold Coast ALS was defined as only upper motor neuron dysfunction. Outcomes, survival time, and progression according to the ALS Functional Rating Scale (ALSFRS-R) were compared with diagnostic categories.
The study population comprised 5957 patients of whom 98.4% met the GCC and 90.0% met the rEEC including 10.1% of patients categorized as Gold Coast ALS and 1.6% categorized as not Gold Coast ALS.
Compared with not Gold Coast, the Gold Coast ALS cohort had almost exclusively spinal onset, a long diagnostic delay, and were mostly men, whereas the not Gold Coast ALS cohort was younger (all P <.001).
Stratified by diagnostic category, the decline in monthly ALSFRS-R score was most rapid among Definite ALS (mean, -1.01 points) followed by Probable ALS (mean, -0.85 points), Probable ALS laboratory-supported (mean, -0.86 points), Possible ALS (mean, -0.72 points), Gold Coast ALS (mean, -0.48 points), and Not Gold Coast ALS (mean, -0.39 points).
Diagnostic category was strongly related with survival time (P <.001). Survival time after diagnosis was shortest for Definite ALS (median, 12.8 mo) followed by Probable ALS (median, 17.5 mo), Probable ALS laboratory-supported (median, 19.4 mo), Possible ALS (median, 22.8 mo), Gold Coast ALS (median, 34.7 mo), and not Gold Coast ALS (median, 69.6 mo).
Within each diagnostic category, there was considerable between-patient variability in the standard deviations for ALSFRS-R (range, 0.32-0.48), forced vital capacity (range, 1.1-1.6), and European Network for the Cure of ALS risk (range, 1.4-2.3). These ranges were largely overlapping, indicating a lack of homogeneity in groups.
This study may have been limited by the complex process of applying the rEEC and the fact that GCC was retrospectively applied.
These data indicated that applying the GCC allowed for more patients to be recruited in a trial and trends in progression and survival differed significantly between groups. However, “Given the large variability per diagnostic category, selecting only specific categories for trials may not result in a more homogeneous study population,” the researchers concluded.
De Jongh AD, Braun N, Weber M, et al. Characterising ALS disease progression according to El Escorial and Gold Coast criteria. J Neurol Neurosurg Psychiatry. Published online June 2, 2022. doi:10.1136/jnnp-2022-328823