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Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease.

Publication ,  Journal Article
Morrow, R; Funk, R; Becker, M; Sherman, A; Van Haandel, L; Hudson, T; Casini, R; Shakhnovich, V
Published in: Pharmaceuticals (Basel, Switzerland)
May 2021

Inside cells, the immunomodulator methotrexate (MTX) undergoes the addition of glutamates to form methotrexate polyglutamates (MTX-Glu)-promising biomarkers of systemic exposure and treatment response to MTX in rheumatology. MTX-Glu are underexplored in Inflammatory Bowel Disease (IBD), with no data in pediatrics. In this cross-sectional secondary analysis, we assessed the relationships between MTX-Glu and MTX dose and treatment response in pediatric IBD. Twenty-one children with IBD, receiving maintenance therapy with infliximab (IFX) and MTX, had MTX-Glu1-6 concentrations and IFX troughs/antibodies measured and disease activity assessed for comparison in remission vs. active IBD using non-parametric tests, with associations explored using Spearman's correlation (ρ) and regression analyses; SASv9.4 (α = 0.05). Total and long-chain MTX-Glu correlated with MTX dose (ρ = 0.51 and 0.56, respectively; p ≤ 0.02). In children with Crohn's disease (n = 19), short-chain MTX-Glu1-2 were 2.5-fold higher in remission vs. active disease, approaching statistical significance (p = 0.066), with no statistical differences in IFX trough (p = 0.549) between groups. Our study highlights a potential role for long-chain MTX-Glu in the therapeutic drug monitoring of MTX in IBD. It is the first study in pediatric IBD and, although statistical significance was not reached, our findings also suggest that higher short-chain MTX-Glu levels may be associated with IBD treatment response to MTX in children.

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Published In

Pharmaceuticals (Basel, Switzerland)

DOI

EISSN

1424-8247

ISSN

1424-8247

Publication Date

May 2021

Volume

14

Issue

5

Start / End Page

463

Related Subject Headings

  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
 

Citation

APA
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Morrow, R., Funk, R., Becker, M., Sherman, A., Van Haandel, L., Hudson, T., … Shakhnovich, V. (2021). Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease. Pharmaceuticals (Basel, Switzerland), 14(5), 463. https://doi.org/10.3390/ph14050463
Morrow, Ryan, Ryan Funk, Mara Becker, Ashley Sherman, Leon Van Haandel, Taina Hudson, Rebecca Casini, and Valentina Shakhnovich. “Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease.Pharmaceuticals (Basel, Switzerland) 14, no. 5 (May 2021): 463. https://doi.org/10.3390/ph14050463.
Morrow R, Funk R, Becker M, Sherman A, Van Haandel L, Hudson T, et al. Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease. Pharmaceuticals (Basel, Switzerland). 2021 May;14(5):463.
Morrow, Ryan, et al. “Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease.Pharmaceuticals (Basel, Switzerland), vol. 14, no. 5, May 2021, p. 463. Epmc, doi:10.3390/ph14050463.
Morrow R, Funk R, Becker M, Sherman A, Van Haandel L, Hudson T, Casini R, Shakhnovich V. Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease. Pharmaceuticals (Basel, Switzerland). 2021 May;14(5):463.

Published In

Pharmaceuticals (Basel, Switzerland)

DOI

EISSN

1424-8247

ISSN

1424-8247

Publication Date

May 2021

Volume

14

Issue

5

Start / End Page

463

Related Subject Headings

  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences