Abstract Details

Title Evaluation of a Health State Staging System Defined by Loss of Independence in Amyotrophic Lateral Sclerosis: Assessment in a Second Dataset

Topic Anterior Horn

Presentation(s) P07 - (-)

Poster/Presentation
Number 066

Objective

Background BACKGROUND: Prognosis in ALS is receiving increased attention with multiple proposals to provide a clearly defined, discrete, and mutually exclusive health state staging system reflecting the clinical progression of ALS. A co-operative international working group has been established to facilitate these efforts and develop general principles for ALS staging systems.

Design/Methods DESIGN/METHODS: We evaluated one proposed staging system that relies upon ALS Functional Rating Scale (ALSFRS) changes in 4 key domains: swallowing, walking/self-care, communicating, and breathing. Impaired functions in each domain were determined by specific ALSFRS item score thresholds. Stages were defined by the number of domains lost (stratified by domain): Stage 0 - functional involvement but no loss of independence on any domain; Stages 1-4 - independence lost in 1-4 domains; Stage 5 - death. We applied this system to data from a randomized ALS creatine study and fit linear mixed models to determine mean trajectories of SF-36 functional health domains by ALS stage.

Results RESULTS: Data from all 175 participants were analyzed. The mean age of ALS onset was 56.3 years (SD=11.1), 67.4% males with mean follow-up of 13.5 months (SD=6.4). At baseline, the distribution of ALS staging was stage 0 (n=108), 1 (n=45), or 2 (n=22). The mean total SF-36 score decreased (p<0.0001) and risk of death increased progressively by ALS stage over follow-up. Physical and mental health domain scores followed similar trends.

Conclusions CONCLUSIONS: This proposed ALS staging approach partitions patients into potentially relevant progression stages, associated with decline in health-related quality of life and an increased risk of death. Independent validation is required to ascertain whether ALS disease progression is appropriately defined to allow the evaluation of therapeutics' effects on different ALS health states.

Authors/Disclosures
PRESENTER	No disclosure on file
Carolyn Young (Biogen UK)	No disclosure on file
Federica Agosta (San Raffaele Scientific Institute)	Federica Agosta has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Philips. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier INC.
Adriano Chio, MD, FAAN (Dept. of Neuroscience, University of Turin)	Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cytokinetics. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Corcept.
Leonard van den Berg, MD (University Medical Centre Utrecht)	The institution of Dr. Van den Berg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amylyx. The institution of Dr. Van den Berg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ferrrer. The institution of Dr. Van den Berg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Van den Berg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Van den Berg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. The institution of Dr. Van den Berg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Van den Berg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. The institution of Dr. Van den Berg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ArgenX. The institution of Dr. Van den Berg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Projenx. Dr. Van den Berg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Corcept. The institution of Dr. Van den Berg has received research support from Netherlands ALS Foundation.
	No disclosure on file
James D. Berry, MD MPH (Massachusetts General Hospital)	Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clene Nanomedicine. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MT Pharma Holdings of America. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Regeneron. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MTPA. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Berry has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Berry has stock in ReactNeuro. The institution of Dr. Berry has received research support from Biogen. The institution of Dr. Berry has received research support from MT Pharma of America. The institution of Dr. Berry has received research support from Rapa Therapeutics. The institution of Dr. Berry has received research support from Brainstorm Cell Therapeutics. The institution of Dr. Berry has received research support from Alexion. The institution of Dr. Berry has received research support from nQ Medical. The institution of Dr. Berry has received research support from ALSA. The institution of Dr. Berry has received research support from MDA. The institution of Dr. Berry has received research support from Amylyx. The institution of Dr. Berry has received research support from Transposon. Dr. Berry has a non-compensated relationship as a Scientific Advisor with Everything ALS that is relevant to AAN interests or activities.
Benjamin R. Brooks, MD, FAAN (Clinical Trials Planning LLC)	Dr. Brooks has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Mitsubishi Tanabe Pharma America. Dr. Brooks has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Medicinova. Dr. Brooks has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Brooks has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AB Science. Dr. Brooks has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis. Dr. Brooks has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Mitsubishi Tanabe Pharma America. The institution of Dr. Brooks has received research support from Mitsubishi TanabePharma America. Dr. Brooks has received personal compensation in the range of $0-$499 for serving as a Member Annual Surveillance Committee CDC National ALS Registry with Center for Disease Control Agency Toxic Substances Disease Registry. Dr. Brooks has a non-compensated relationship as a Member ALS Quality Measures Subcommittee with ��ɫ�� that is relevant to AAN interests or activities.
Jeremy M. Shefner, MD, PhD, FAAN (Barrow Neurological Institute)	Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Uniqure. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clene. Dr. Shefner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cytokinetics. Dr. Shefner has received personal compensation in the range of $0-$499 for serving as a Consultant for Mitsubishi Tanabe Pharma America. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for annexon. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurosense. Dr. Shefner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neuvivo. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nura BIo. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prilenia. Dr. Shefner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for swanbio. Dr. Shefner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vertex. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Shefner has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for UpToDate. The institution of Dr. Shefner has received research support from NIH. The institution of Dr. Shefner has received research support from Mitsubishi Tanabe Pharma America. The institution of Dr. Shefner has received research support from Amylyx. The institution of Dr. Shefner has received research support from BIogen. The institution of Dr. Shefner has received research support from Cytokinetics. The institution of Dr. Shefner has received research support from IONIS. The institution of Dr. Shefner has received research support from Healey Center for ALS. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a grant review chair with DOD- General Dynamics.
Martin R. Turner, MBBS, PhD, MA, FRCP (University of Oxford)	No disclosure on file
James R. Williams III, PhD	Dr. Williams has received personal compensation for serving as an employee of Biogen. Dr. Williams has received stock or an ownership interest from Biogen.
	No disclosure on file
Douglas A. Kerr, MD, PhD	Dr. Kerr has received personal compensation for serving as an employee of Dyne Therapeutics. Dr. Kerr has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BlueRock Therapeutics. Dr. Kerr has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Trace Neuroscience. Dr. Kerr has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Spolia Therapeutics. Dr. Kerr has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for BlueRock Therapeutics. Dr. Kerr has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for AAVantgarde Therrapeutics. Dr. Kerr has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Trace Neuroscience. Dr. Kerr has or had stock in Dyne Therapeutics.

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