Predictors of Outcome in Amyotrophic Lateral Sclerosis (P2.076)

OBJECTIVE: To evaluate predictors of outcome in Amyotrophic Lateral Sclerosis (ALS) using a large patient cohort who underwent longitudinal standardized assessments. BACKGROUND: Improved disease progression prognostication in ALS would guide patient care and improve statistical power of trials. DESIGN/METHODS: Data were collected from the Ceftriaxone in ALS trial database (n=513, mean follow-up days=584+/-351). Outcomes included: ALS Functional Rating Scale-Revised (ALSFRS-R), Forced Vital Capacity (FVC), upper and lower limb hand held dinamometry megascores (HHD), tracheostomy-free survival. Predictors considered were: gender, age, site of onset (bulbar, limb), Definite El Escorial Criteria (EEC), diagnostic delay, disease duration, baseline creatinine, bicarbonate and body max index (BMI). Random slopes models and Cox models were used to study baseline predictors of these outcome measures after controlling for treatment. RESULTS: ALSFRS-R and FVC decline was slower in limb onset (difference=0.23/p=0.0162; difference=0.96/p=0.0022), non-Definite EEC (difference=0.24/p=0.0015; difference=0.81/p=0.0012), younger age/year (difference=0.01/p=0.0060; difference=0.04/p=0.0006); and as disease duration at baseline (difference=0.39/p<.0001; difference=0.85/p<.0001) and diagnostic delay (difference=0.39/p<.0001; difference=0.99/p<.0001) increased/year. FVC decline was also slower as creatinine (difference=1.37/p=0.0463) increased per mg/dL. Upper limb HHD progression was slower in females (difference=1.16/p=0.0015); as baseline bicarbonate (difference=1.98/p=0.0069) increased per mEq/L; and as disease duration (difference=0.84/p=0.0017) and diagnostic delay (difference=1.31/p<.0001) increased/year. Lower limb HHD decline was slower in baseline BMI>30 (difference=1.3418/p=0.0177), non-Definite EEC (difference=0.92/p=0.0328); as baseline creatinine (difference=4.84/p<.0001) increased per mg/dL; and as disease duration (difference=0.85/p=0.0079) and diagnostic delay (difference=1.24/p=0.0015) increased/year. Longer tracheostomy-free survival was associated with limb onset (HR=0.70/p=0.0132), non-Definite EEC (HR=0.74/p=0.0117), younger age (p<.0001), higher baseline creatinine (HR=0.45/p=0.0188), and longer baseline disease duration (HR=0.74/p=0.0009) and diagnostic delay (HR=0.76/p=0.0150). CONCLUSIONS: We confirmed that slower disease progression is associated with limb onset, younger age, non-Definite EEC and increased diagnostic delay and BMI. We identified higher baseline creatinine and bicarbonate as predictors of slower course. Additional studies are needed to assess the potential mechanisms underlying these associations. Study Supported by: National Institute of Health (NIH) Disclosure: Dr. Ratti has nothing to disclose. Dr. Berry has received personal compensation for activities with Oakstone Publishing, the Muscular Dystrophy Association, and ALS Therapy Alliance. Dr. Atassi has received personal compensation for activities with Biogen Idec. Dr. Shui has nothing to disclose. Dr. Hayden has nothing to disclose. Dr. Schoenfeld has received personal compensation for activities with Seno, Galenabio, Alexion, Edison, Anika, Hemispherix, Zs-pharma, Aptalis, Mylan, Biogen Idec, Spinal, Polymedico, Exact, and Qmed. Dr. Yu has nothing to disclose. Dr. Conwit has nothing to disclose. Dr. Cudkowicz has received personal compensation for activities with Trophos, GlaxoSmithKline Inc., Biogen Idec, and Teva Neuroscience. Dr. Cudkowicz has received research support from Biogen Idec, and Neuraltis.