Dextromethorphan-Quinidine (Nuedexta) Improves Swallowing in Bulbar Onset ALS Patients with Pseudobulbar Affect - Pre-Post Observational Study in 86 ALS Patients (P4.4-019)

Objective: To present data on effect of DMq treatment on swallowing in 86 ALS patients treated for PBA. Background: Dextramethorphan-20mg-Quinidine-10mg(Nuedexta)[DMq]has been approved by the Food and Drug Administration for treatment of pseudobulbar affect[PBA]in multiple conditions[Pioro et al, 2010]. A small observational single arm clinical trial identified benefit of DMq on swallowing in 15 of 29 ALS patients[Wright et al, 2016]. A recent randomized cross-over clinical trial of DMq versus placebo indicated a significant clinical effect of DMq treatment on speech and swallowing in ALS patients[Smith et al, 2017]. Design/Methods: DMq was given to 86 ALS patients to treat PBA and their pre- and post- swallowing rates for 90 mL of water were recorded approximately 4–8 weeks apart. Measurements included number of breaths taken, swallow time in seconds, number of swallows, and if any coughs or clearings of the throat. Patients completed Center for Neurologic Study-Lability Scale(CNS-LS)for pseudobulbar affect and the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised(ALSFRS-R). Statistical analysis was completed with MedCalc (Ostend, Belgium). Results: Liquid Swallowing (90mL water) Rate [ LSR ] improved statistically significantly in the patient group overall from median LSR=4.16 mL/sec (95%CI−3.30–5.22) to median LSR= 5.43 L/min (95 % CI=4.28–6.65) [ Wilcoxan paired P=0.0091 ]. Conclusions: DMq treatment is associated with increased LSR swallowing capacity in 54 / 86 ( 63 % ) ALS patients with PBA. In 35 / 86 ( 41 % ) DMq treated ALS patients with PBA improving more than 20% above pre-treatment, the LSR improved + 49 % ( 95 % CI = +40 to +58 %) compared with + 16 % ( 95 % CI = +12 to +19 %) in those 19 / 86 ( 22 % ) who showed less than 20% improvement. LSR improvement was not associated with a self-report of improvement in ALSFRS-R Swallowing Item score and a preponderance of the > 20 % LSR improvement responders were bulbar onset patients. Disclosure: Dr. Shah has nothing to disclose. Dr. Wright has nothing to disclose. Dr. Bravver has received research support from Acceleron, Marathon, Cytokinetics, Biohaven, Orion. Dr. Desai has received research support from Acceleron, Cytokinetics, Biohaven, and Orion. Dr. Langford has nothing to disclose. Dr. Bockenek has nothing to disclose. Dr. Lindblom has nothing to disclose. Dr. Linville has nothing to disclose. Dr. Paling has nothing to disclose. Dr. Williamson has nothing to disclose. Dr. Brooks has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Mitsubishi Tanabe Pharma USA, Biohaven, Cytokinetics, ITF Pharma, . Dr. Brooks has received personal compensation in an editorial capacity for American Journal of Managed Care. Dr. Brooks has received research support from Medicinova, Neuraltus, Cytokinetics,Santhera, Biogen, ITF Pharma, Acceleron, Center for Disease Control, Orion, Biohaven.