Serum urate at trial entry and ALS progression in EMPOWER.
Our objective was to determine whether serum urate predicts ALS progression. A study population comprised adult participants of EMPOWER (n = 942), a phase III clinical trial to evaluate the efficacy of dexpramipexole to treat ALS. Urate was measured in blood samples collected during enrollment as part of the routine block chemistry. We measured outcomes by combined assessment of function and survival rank (CAFs), and time to death, by 12 months. Results showed that in females there was not a significant relation between urate and outcomes. In males, outcomes improved with increasing urate (comparing highest to lowest urate quartile: CAFS was 53 points better with p for trend = 0.04; and hazard ratio for death was 0.60 with p for trend = 0.07), but with adjustment for body mass index (BMI) at baseline, a predictor of both urate levels and prognosis, associations were attenuated and no longer statistically significant. Overall, participants with urate levels equal to or above the median (5.1 mg/dl) appeared to have a survival advantage compared to those below (hazard ratio adjusted for BMI: 0.67; 95% confidence interval 0.47-0.95). In conclusion, these findings suggest that while the association between urate at baseline and ALS progression is partially explained by BMI, there may be an independent beneficial effect of urate.
a Department of Nutrition, Harvard TH Chan School of Public Health, Boston. Channing Division of Network Medicine , Harvard Medical School and Brigham and Women's Hospital , Boston , Massachusetts.
ÉIlis J
ÉJ
O'Reilly
b ALS Neuroscience Discovery and Development , Biogen , Cambridge , Massachusetts.
Dawei
D
Liu
b ALS Neuroscience Discovery and Development , Biogen , Cambridge , Massachusetts.
Donald R
DR
Johns
c Department of Neurology , Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease , Boston , Massachusetts.
Merit E
ME
Cudkowicz
c Department of Neurology , Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease , Boston , Massachusetts.|d Department of Physical Medicine and Rehabilitation , Harvard Medical School, Spaulding Rehabilitation Hospital , Boston, Massachusetts; VA Healthcare System , Boston , Massachusetts , and.
Sabrina
S
Paganoni
c Department of Neurology , Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease , Boston , Massachusetts.
Michael A
MA
Schwarzschild
b ALS Neuroscience Discovery and Development , Biogen , Cambridge , Massachusetts.
Melanie
M
Leitner
e Department of Epidemiology and Nutrition , Harvard TH Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Harvard Medical School and Brigham and Women's Hospital , Boston , Massachusetts , USA.
Alberto
A
Ascherio
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000188:drug therapy*; D000975:Antioxidants / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D000077487:Pramipexole; D012737:Sex Factors; D016019:Survival Analysis; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
D000975:Antioxidants; D052160:Benzothiazoles; D014527:Uric Acid; D000077487:Pramipexole
Survival; biomarkers; body mass index; progression; urate
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