Supplementary Material for: Estimating Amyotrophic Lateral Sclerosis and Motor Neuron Disease Prevalence in Portugal Using a Pharmaco-Epidemiological Approach and a Bayesian Multiparameter Evidence Synthesis Model

Background: Amyotrophic lateral sclerosis (ALS) is a rare and progressive neurodegenerative disease involving the upper and lower motor neurons. It is also the most common and the one with the worst prognosis among the motor neuron diseases (MND). ALS invariably progresses to respiratory failure, which is an essential factor affecting the prognosis of this disease. Its prevalence in the world is heterogeneous and, in many countries, is even unknown, since national registries are not mandatory or comprehensive enough. Worldwide, the ALS/MND prevalence is estimated between 4 and 8 cases per 100,000 inhabitants, but in Portugal the prevalence was never studied. Because ALS and MND are rare diseases, population-based studies are very difficult to perform. In Portugal, there are no systematic patient registries. Objective: We aimed to obtain the best available indirect estimates of ALS/MND prevalence, using a pharmaco-epidemiological approach. Method: We developed a Bayesian multiparameter evidence synthesis model based on nationwide data of riluzole consumption, a drug highly specific for ALS/MND, combined with data from a nationwide hospital administrative database, data from the national institute of statistics, and data from other scientific articles focused on ALS/MND epidemiology, to estimate ALS/MND prevalence in Portugal. Results: We found an estimated ALS/MND prevalence in Portugal steadily increasing from 6.74 per 100,000 inhabitants (Bayesian 95% Credible Interval [95% CI] 5.39–9.37) in 2009 to 10.32 (95% CI 8.27–14.27) in 2016. In 2016, the estimated ALS/MND prevalence was higher in men, 12.08 per 100,000 (9.66–17.15), than in women, 8.56 (6.84–12.32). Regarding age groups, the estimated prevalence per 100,000 inhabitants were, in 2016 for women, 1.19 (0.78–1.85) for the <50 years’ group, 8.48 (6.00–12.76) for the 51–60 group, 23.47 (18.05–33.88) for the 61–70 group, 28.77 (22.02–41.31) for the 71–80 group, and 14.45 (9.97–21.63) for the >80 group. For men, the prevalence estimates were 1.90 (1.32–2.84), 12.89 (9.44–19.16), 32.18 (24.91–45.74), 48.85 (38.72–71.40), and 31.27 (21.73–46.41), respectively, for each age group. We also observed a relevant variability across the country, with prevalence estimates, in 2016, of 9.31 cases per 100,000 inhabitants (7.45–12.86) in the Northern region of Portugal, 11.15 (8.9–15.34) in the Centre region, 10.74 (8.6–14.82) in Lisbon and Alentejo regions, and 5.55 (4.35–7.83) in the Algarve region. Conclusion: Overall, and even though we must account for the limitations of the indirect methods and models used for prevalence estimation, we probably have a very high ALS/MND prevalence in Portugal. It would be important to create registries, particularly in rare diseases, for better organization and distribution of healthcare services and resources, particularly at the level of ventilatory support.