Methotrexate Polyglutamation in a Myasthenia Gravis Clinical Trial.
Abstract
Introduction:Methotrexate (MTX) is an immunosuppressive and anti-inflammatory drug
used to treat rheumatoid arthritis (RA) and other autoimmune conditions. MTX is transported
into cells, where glutamate moieties are added and is retained as methotrexate polyglutamates
(MTXPGs). In the RA literature, it has been reported that the degree of polyglutamation
correlates with the anti-inflammatory effect of MTX in RA. There are no prior studies
evaluating the relationship between MTXPGs and myasthenia gravis (MG) outcome measures.
The objective of this study was to assess the correlation between methotrexate (MTX)
polyglutamates (MTXPGs) with Myasthenia Gravis (MG) outcome measures. Methods:An analysis
was done of blood drawn from patients enrolled in the 12-month randomized, placebo-controlled
study of MTX in MG study. Red blood cell MTXPGs were measured via ultra-performance
liquid chromatography and tandem mass spectrometry. MTXPG was correlated to MG outcome
measures using Spearman Correlation Coefficient. A two-group t-test was used to determine
the difference in MTXPG based on clinical outcome responder definitions. Results:Twenty-one
polyglutamate samples were analyzed of subjects on MTX while eight samples were analyzed
from subjects on placebo. Pentaglutamate had the strongest correlation with the MG-ADL
(0.99), while tetraglutamate had the strongest correlation with the QMG (0.54). Triglutamate
had the strongest correlation with MGC (0.76). Conclusion:There were variable correlations
between MTXPG1-5 and MG outcomes (rho range: 0.08 to 0.99). There are strong correlations
between MTXPG and the MG-ADL, QMG, and MGC. Long chain methotrexate polyglutamates
correlate better with MG outcomes.
Type
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Show full item recordScholars@Duke
Mara Becker
Professor of Pediatrics
Dr. Becker is currently a Professor of Pediatrics and the Vice Dean for Faculty at
Duke University School of Medicine. Prior to arriving at Duke in 2019, she spent 13
years at Children’s Mercy, Kansas City where she completed additional fellowship training
in pediatric clinical pharmacology and served as Division Director of Rheumatology
and Associate Chair for the Department of Pediatrics. At Duke, Dr. Becker served as
the Vice Chair for Faculty in Pediatrics, until she assumed the rol

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