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Methotrexate Polyglutamation in a Myasthenia Gravis Clinical Trial.

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Date
2020-01
Authors
Pasnoor, Mamatha
Heim, Andrew J
Herbelin, Laura
Statland, Jeffrey
Dimachkie, Mazen M
Becker, Mara
Barohn, Richard J
Methotrexate in MG Investigators of the Muscle Group Study
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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
Journal article
Subject
Methotrexate in MG Investigators of the Muscle Group Study
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https://hdl.handle.net/10161/20591
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Scholars@Duke

Becker

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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