METABOLIC EFFECTS OF THE STEROID ANTIBIOTIC FUSIDIC ACID.

Abstract

OBJECTIVE: We aim to further evaluate survival differences and disease progression based on urate levels in a larger cohort of ALS patients. BACKGROUND: Low blood levels of urate (uric acid) have been demonstrated in patients with ALS. A dose-dependent survival advantage in men with higher baseline urate levels has also been shown, while no advantage was observed in women. DESIGN/METHODS: Pooled data of 1767 subjects with ALS (1,093 men, 674 women) from the PRO-ACT database were available for analysis. Random slopes and Cox proportional hazards regression models, adjusted for baseline predictors of disease severity, were used to evaluate associations between urate levels and ALSFRS-R decline and survival, respectively. RESULTS: Mean baseline urate levels differed significantly by gender (p&lt;0.001) and were significantly lower in women than men (4.2mg/dL and 5.4mg/dL respectively, difference in means -1.2). The change in urate levels over time did not differ significantly by gender (p=0.34). Baseline urate levels were significantly associated with weight (p&lt;0.0001) and creatinine (p&lt;0.0001). Multivariate analysis controlling for predictors of disease severity as well as urate*gender interaction, creatinine, and weight demonstrated that higher levels of urate at baseline were associated with slower ALSFRS-R decline over 1 year (p=0.01, difference = -0.07 decline in ALSFRS-R scores per month for each unit increase in urate levels). In multivariate analysis, the risk of dying of ALS over 1 year decreased by 11[percnt] (HR 0.89, 95[percnt] CI (0.81,0.98), p=0.01) for each unit (mg/dL) increase in baseline urate. When baseline weight was included as a co-variate, however, the survival models were no longer statistically significant. CONCLUSION: Our pooled analysis provides further support to urate levels as a prognostic factor in ALS and confirms the utility of the PRO-ACT database as a powerful resource for ALS epidemiological research. <b>Disclosure:</b> Dr. Nicholson has nothing to disclose. Dr. Paganoni has nothing to disclose. Dr. Shui has nothing to disclose. Dr. Schoenfeld has received personal compensation for activities with Seno, Galena Biopharma, Alexion Pharmaceuticals, Edison Pharmaceuticals, Anika Therapeutics, Hemispherix Biopharma, ZS Pharma, Inc., Aptalis, Mylan, Biogen Idec, Spinal, Polymedico, Inc Dr. Sherman has nothing to disclose. Dr. Berry has received personal compensation for activities with Oakstone Publishing as a speaker. Dr. Berry has received research support from the Muscular Dystrophy Association and ALS Therapy Alliance. Dr. Cudkowicz has received personal compensation for activities with GlaxoSmithKline, Biogen Idec, Teva Neuroscience, and Cytokinetics. Dr. Cudkowicz has received personal compensation in an editorial capacity for JAMA Neurology. Dr. Atassi has received personal compensation for activities with Biogen Idec as a consultant.