Serum Uric Acid and Amyotrophic Lateral Sclerosis Progression: An Exploratory Analysis of Potential Riluzole Interaction

ABSTRACT Objective To explore the association between serum uric acid (UA) and disease progression in amyotrophic lateral sclerosis (ALS), and to evaluate whether riluzole modifies this association. Methods In this single‐center retrospective cohort study, baseline UA was analyzed in 351 patients with sporadic ALS. Functional decline (ΔALSFRS‐R/m) was assessed using Spearman correlations in 91 complete cases, with Bonferroni correction, and by multivariable linear regression including a UA × riluzole interaction term. Survival was assessed from symptom onset using Kaplan–Meier and Cox methods, with death or invasive mechanical ventilation as the composite endpoint. Results Of 351 patients, 89 (25.4%) used riluzole. UA was not significantly correlated with baseline ALSFRS‐R (Pearson r = 0.083, p = 0.119) or ΔALSFRS‐R/m (Spearman r = −0.023, p = 0.832), including riluzole‐treated, untreated, male, and female subgroups. The UA × riluzole interaction was not significant (β = −0.018, 95% CI: −0.043 to 0.006, p = 0.146), and no significant associations were found with BMI, age at onset, MRC score, or FVC%. During follow‐up, 160 patients (45.6%) reached the composite endpoint; survival did not differ by riluzole use, UA group, or sex. Conclusion Baseline UA was not significantly associated with functional decline or survival, and riluzole did not significantly modify the UA–progression association. Larger multicenter studies with repeated UA measurements are warranted.