Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/5/463 |
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| author | Ryan Morrow Ryan Funk Mara Becker Ashley Sherman Leon Van Haandel Taina Hudson Rebecca Casini Valentina Shakhnovich |
| author_facet | Ryan Morrow Ryan Funk Mara Becker Ashley Sherman Leon Van Haandel Taina Hudson Rebecca Casini Valentina Shakhnovich |
| author_sort | Ryan Morrow |
| collection | DOAJ |
| description | 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-Glu<sub>1–6</sub> 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; <i>p</i> ≤ 0.02). In children with Crohn’s disease (<i>n</i> = 19), short-chain MTX-Glu<sub>1–2</sub> were 2.5-fold higher in remission vs. active disease, approaching statistical significance (<i>p</i> = 0.066), with no statistical differences in IFX trough (<i>p</i> = 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. |
| first_indexed | 2024-03-10T11:24:43Z |
| format | Article |
| id | doaj.art-485091928624434bacae4058090f0401 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T11:24:43Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-485091928624434bacae4058090f04012023-11-21T19:44:32ZengMDPI AGPharmaceuticals1424-82472021-05-0114546310.3390/ph14050463Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel DiseaseRyan Morrow0Ryan Funk1Mara Becker2Ashley Sherman3Leon Van Haandel4Taina Hudson5Rebecca Casini6Valentina Shakhnovich7Children’s Mercy Kansas City, Kansas City, MO 64108, USADepartment of Pharmacy Practice, University of Kansas, Kansas City, KS 60047, USADepartment of Pediatrics, Duke University Hospital, Durham, NC 27705, USAChildren’s Mercy Kansas City, Kansas City, MO 64108, USAAbbvie Pharmaceuticals, North Chicago, IL 60085, USAChildren’s Mercy Kansas City, Kansas City, MO 64108, USANorthShore University Health System, Skokie, IL 60201, USAChildren’s Mercy Kansas City, Kansas City, MO 64108, USAInside 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-Glu<sub>1–6</sub> 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; <i>p</i> ≤ 0.02). In children with Crohn’s disease (<i>n</i> = 19), short-chain MTX-Glu<sub>1–2</sub> were 2.5-fold higher in remission vs. active disease, approaching statistical significance (<i>p</i> = 0.066), with no statistical differences in IFX trough (<i>p</i> = 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.https://www.mdpi.com/1424-8247/14/5/463methotrexatemethotrexate polyglutamatesinfliximabinflammatory bowel diseaseCrohn’s diseaseulcerative colitis |
| spellingShingle | Ryan Morrow Ryan Funk Mara Becker Ashley Sherman Leon Van Haandel Taina Hudson Rebecca Casini Valentina Shakhnovich Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease Pharmaceuticals methotrexate methotrexate polyglutamates infliximab inflammatory bowel disease Crohn’s disease ulcerative colitis |
| title | Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease |
| title_full | Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease |
| title_fullStr | Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease |
| title_full_unstemmed | Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease |
| title_short | Potential Role of Methotrexate Polyglutamates in Therapeutic Drug Monitoring for Pediatric Inflammatory Bowel Disease |
| title_sort | potential role of methotrexate polyglutamates in therapeutic drug monitoring for pediatric inflammatory bowel disease |
| topic | methotrexate methotrexate polyglutamates infliximab inflammatory bowel disease Crohn’s disease ulcerative colitis |
| url | https://www.mdpi.com/1424-8247/14/5/463 |
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