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Pharmaceuticals
Volume 14
Issue 5
10.3390/ph14050463
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Article

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

by
Ryan Morrow
1,2,*,
Ryan Funk
3,
Mara Becker
4,
Ashley Sherman
1,2,
Leon Van Haandel
5,
Taina Hudson
1,2,
Rebecca Casini
6 and
Valentina Shakhnovich
1,2
1
Children’s Mercy Kansas City, Kansas City, MO 64108, USA
2
University of Missouri Kansas City School of Medicine, Kansas City, MO 64108, USA
3
Department of Pharmacy Practice, University of Kansas, Kansas City, KS 60047, USA
4
Department of Pediatrics, Duke University Hospital, Durham, NC 27705, USA
5
Abbvie Pharmaceuticals, North Chicago, IL 60085, USA
6
NorthShore University Health System, Skokie, IL 60201, USA
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2021, 14(5), 463; https://doi.org/10.3390/ph14050463
Submission received: 28 February 2021 / Revised: 9 May 2021 / Accepted: 10 May 2021 / Published: 14 May 2021
(This article belongs to the Special Issue Drugs and Treatments for Inflammatory Bowel Diseases)
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Abstract

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.
Keywords: methotrexate; methotrexate polyglutamates; infliximab; inflammatory bowel disease; Crohn’s disease; ulcerative colitis; pediatric methotrexate; methotrexate polyglutamates; infliximab; inflammatory bowel disease; Crohn’s disease; ulcerative colitis; pediatric

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MDPI and ACS Style

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 2021, 14, 463. https://doi.org/10.3390/ph14050463

AMA Style

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. 2021; 14(5):463. https://doi.org/10.3390/ph14050463

Chicago/Turabian Style

Morrow, Ryan, Ryan Funk, Mara Becker, Ashley Sherman, Leon Van Haandel, Taina Hudson, Rebecca Casini, and Valentina Shakhnovich. 2021. "Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease" Pharmaceuticals 14, no. 5: 463. https://doi.org/10.3390/ph14050463

APA Style

Morrow, R., Funk, R., Becker, M., Sherman, A., Van Haandel, L., Hudson, T., Casini, R., & Shakhnovich, V. (2021). Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease. Pharmaceuticals, 14(5), 463. https://doi.org/10.3390/ph14050463

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