Abstract

We sought to examine the influence of medication usage and laboratory measurements on disease progression in amyotrophic lateral sclerosis (ALS). A database of 596 volunteers with ALS was generated from three clinical trials and one observational study. Disease course was measured by survival and three functional measures: the ALS Functional Rating Scale (ALSFRS), Vital Capacity (VC) and Maximum Voluntary Isometric Contraction (MVIC). Survival modeling was performed using Cox proportional hazards regression. The association of medication or laboratory measurements with disease progression was determined using a random effects model. In the multivariate analysis, survival was shorter in participants who took aspirin (HR =1.93, p =0.046); NSAIDs (HR =1.51, p =0.054); had low blood chloride (HR =0.76, p =0.020) or high bicarbonate levels (HR =1.37, p =0.006). Individuals who took calcium had better survival (HR =0.37, p =0.008) and a slower rate of decline of MVIC arm megascore (p =0.033). Vital capacity declined faster in individuals with lower serum chloride (p<0.0001), or higher bicarbonate (p =0.002) levels and those taking paracetamol (acetaminophen) (p =0.035). We conclude that aspirin or NSAID use may shorten survival in ALS, while calcium use may prolong survival. Our results support a need to further explore the role of neuroinflammation in the pathogenesis of ALS.

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