Genetic biomarkers of methotrexate response and safety in Crohn's disease : Data from the Spanish ENEIDA registry
© 2024 British Pharmacological Society..
AIMS: Methotrexate (MTX) is used to induce and maintain remission in patients with steroid-dependent Crohn's disease (CD). Despite its proven efficacy, its use is limited due to associated adverse events. Polymorphisms involving folate pathway genes might influence MTX efficacy and toxicity. We aimed to assess the impact of certain polymorphisms on the therapeutic outcomes of MTX in CD.
METHODS: Patients with CD who exclusively followed MTX monotherapy and fulfilled inclusion criteria were identified from the GETECCU ENEIDA registry. Variants of ATIC, DHFR, MTHFR, SLC19A1, ABCB1 and ABCC3 genes were analysed and their association with efficacy and toxicity was assessed.
RESULTS: A total of 129 patients were included in the analysis. MTX was used at a median weekly dose of 25 mg (interquartile range, 15-25 mg) and a median time of 14 months (interquartile range, 4-52 months). Thirty-seven percent of the patients achieved disease remission with MTX monotherapy, while 34% were nonresponders (MTX failure). MTX-related toxicity occurred in 40 patients (30%), leading to MTX discontinuation in 19%. DHFR rs408626 (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.22-7.69; P = .017) and MTHFR rs1801133 (OR 2.86, 95% CI 1.23-6.68; P = .015) variants, and smoking (OR 2.61, 95% CI 1.12-6.05; P = .026) were associated with a higher risk of MTX failure. Additionally, the MTHFR rs1801131 variant was associated with a higher risk of MTX-related adverse effects (OR 2.78, 95% CI 1.26-6.13, P = .011).
CONCLUSION: Our study shows that variants of MTHFR and DHFR genes may be associated with MTX efficacy and adverse events in patients with CD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:90 |
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| Enthalten in: |
British journal of clinical pharmacology - 90(2024), 5 vom: 27. Apr., Seite 1301-1311 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Salazar, Juliana [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.04.2024 Date Revised 29.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/bcp.16017 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368597482 |
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| 100 | 1 | |a Salazar, Juliana |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genetic biomarkers of methotrexate response and safety in Crohn's disease |b Data from the Spanish ENEIDA registry |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 29.04.2024 | ||
| 500 | |a Date Revised 29.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 British Pharmacological Society. | ||
| 520 | |a AIMS: Methotrexate (MTX) is used to induce and maintain remission in patients with steroid-dependent Crohn's disease (CD). Despite its proven efficacy, its use is limited due to associated adverse events. Polymorphisms involving folate pathway genes might influence MTX efficacy and toxicity. We aimed to assess the impact of certain polymorphisms on the therapeutic outcomes of MTX in CD | ||
| 520 | |a METHODS: Patients with CD who exclusively followed MTX monotherapy and fulfilled inclusion criteria were identified from the GETECCU ENEIDA registry. Variants of ATIC, DHFR, MTHFR, SLC19A1, ABCB1 and ABCC3 genes were analysed and their association with efficacy and toxicity was assessed | ||
| 520 | |a RESULTS: A total of 129 patients were included in the analysis. MTX was used at a median weekly dose of 25 mg (interquartile range, 15-25 mg) and a median time of 14 months (interquartile range, 4-52 months). Thirty-seven percent of the patients achieved disease remission with MTX monotherapy, while 34% were nonresponders (MTX failure). MTX-related toxicity occurred in 40 patients (30%), leading to MTX discontinuation in 19%. DHFR rs408626 (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.22-7.69; P = .017) and MTHFR rs1801133 (OR 2.86, 95% CI 1.23-6.68; P = .015) variants, and smoking (OR 2.61, 95% CI 1.12-6.05; P = .026) were associated with a higher risk of MTX failure. Additionally, the MTHFR rs1801131 variant was associated with a higher risk of MTX-related adverse effects (OR 2.78, 95% CI 1.26-6.13, P = .011) | ||
| 520 | |a CONCLUSION: Our study shows that variants of MTHFR and DHFR genes may be associated with MTX efficacy and adverse events in patients with CD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Crohn's disease | |
| 650 | 4 | |a efficacy | |
| 650 | 4 | |a methotrexate | |
| 650 | 4 | |a pharmacogenetics | |
| 650 | 4 | |a polymorphisms | |
| 650 | 4 | |a toxicity | |
| 650 | 7 | |a Methotrexate |2 NLM | |
| 650 | 7 | |a YL5FZ2Y5U1 |2 NLM | |
| 650 | 7 | |a Genetic Markers |2 NLM | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Methylenetetrahydrofolate Reductase (NADPH2) |2 NLM | |
| 650 | 7 | |a EC 1.5.1.20 |2 NLM | |
| 700 | 1 | |a Garcia-Planella, Esther |e verfasserin |4 aut | |
| 700 | 1 | |a Fernández-Clotet, Agnès |e verfasserin |4 aut | |
| 700 | 1 | |a Esteve, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Gisbert, Javier P |e verfasserin |4 aut | |
| 700 | 1 | |a Busquets, David |e verfasserin |4 aut | |
| 700 | 1 | |a Lucendo, Alfredo |e verfasserin |4 aut | |
| 700 | 1 | |a Márquez, Lucía |e verfasserin |4 aut | |
| 700 | 1 | |a Guardiola, Jordi |e verfasserin |4 aut | |
| 700 | 1 | |a Martín-Arranz, María Dolores |e verfasserin |4 aut | |
| 700 | 1 | |a Iglesias, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Monfort, David |e verfasserin |4 aut | |
| 700 | 1 | |a Villoria, Albert |e verfasserin |4 aut | |
| 700 | 1 | |a Cañete, Fiorella |e verfasserin |4 aut | |
| 700 | 1 | |a Bell, Olga |e verfasserin |4 aut | |
| 700 | 1 | |a Ricart, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Zabana, Yamile |e verfasserin |4 aut | |
| 700 | 1 | |a Chaparro, María |e verfasserin |4 aut | |
| 700 | 1 | |a Domènech, Eugeni |e verfasserin |4 aut | |
| 700 | 1 | |a Gordillo, Jordi |e verfasserin |4 aut | |
| 700 | 0 | |a ENEIDA registry of GETECCU |e verfasserin |4 aut | |
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