More Dose-dependent Side Effects with Mercaptopurine over Azathioprine in IBD Treatment Due to Relatively Higher Dosing
BACKGROUND: There are substantial global differences in the preference for mercaptopurine (MP) or its prodrug azathioprine (AZA) as first-choice thiopurine to treat inflammatory bowel diseases. Studies comparing both agents are scarce. Our aim was to compare AZA and MP in thiopurine-naive patients with inflammatory bowel disease for the frequency of side effects and efficacy.
METHODS: Post hoc analysis of the "Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory bowel disease Clinics" (TOPIC) trial, in which thiopurine-naive patients with inflammatory bowel disease with an indication for a thiopurine were randomized for a genotype-based dose versus standard of care. For this study, Cox proportional hazard ratios (HRs) were calculated to compare AZA and MP for discontinuation rates within 5 months, incidence of hepatotoxicity, leukopenia, and gastrointestinal side effects. Treatment efficacy was compared by logistic regression.
RESULTS: Patient characteristics were similar for patients treated with AZA (n = 494, 64.4%) and MP (n = 273, 35.6%), yet patients with MP were relatively higher dosed compared with those on AZA. Discontinuation rates within 5 months were not different, 39.3% (AZA) and 38.1% (MP), HR 0.92 (95% confidence interval, 0.72-1.17; P = 0.50); however, patients on MP were more often subjected to dose reductions (30% versus 14%, P < 0.01). Higher rates of hepatotoxicity, HR 1.93 (95% confidence interval, 1.35-2.76; P < 0.01) and leukopenia, HR 2.55 (95% confidence interval, 1.51-4.30; P < 0.01) were observed with MP, which annulled in a secondary analysis with adjustment for the higher dose and metabolite levels.
CONCLUSIONS: Patients treated with MP were relatively higher dosed, which resulted in more dose-dependent side effects and a higher rate of dose reductions.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Inflammatory bowel diseases - 23(2017), 10 vom: 21. Okt., Seite 1873-1881 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Broekman, Mark M T J [VerfasserIn] |
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| Links: |
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| Themen: |
Azathioprine |
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| Anmerkungen: |
Date Completed 31.05.2018 Date Revised 13.11.2018 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/MIB.0000000000001163 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM273220578 |
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| 100 | 1 | |a Broekman, Mark M T J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a More Dose-dependent Side Effects with Mercaptopurine over Azathioprine in IBD Treatment Due to Relatively Higher Dosing |
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| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: There are substantial global differences in the preference for mercaptopurine (MP) or its prodrug azathioprine (AZA) as first-choice thiopurine to treat inflammatory bowel diseases. Studies comparing both agents are scarce. Our aim was to compare AZA and MP in thiopurine-naive patients with inflammatory bowel disease for the frequency of side effects and efficacy | ||
| 520 | |a METHODS: Post hoc analysis of the "Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory bowel disease Clinics" (TOPIC) trial, in which thiopurine-naive patients with inflammatory bowel disease with an indication for a thiopurine were randomized for a genotype-based dose versus standard of care. For this study, Cox proportional hazard ratios (HRs) were calculated to compare AZA and MP for discontinuation rates within 5 months, incidence of hepatotoxicity, leukopenia, and gastrointestinal side effects. Treatment efficacy was compared by logistic regression | ||
| 520 | |a RESULTS: Patient characteristics were similar for patients treated with AZA (n = 494, 64.4%) and MP (n = 273, 35.6%), yet patients with MP were relatively higher dosed compared with those on AZA. Discontinuation rates within 5 months were not different, 39.3% (AZA) and 38.1% (MP), HR 0.92 (95% confidence interval, 0.72-1.17; P = 0.50); however, patients on MP were more often subjected to dose reductions (30% versus 14%, P < 0.01). Higher rates of hepatotoxicity, HR 1.93 (95% confidence interval, 1.35-2.76; P < 0.01) and leukopenia, HR 2.55 (95% confidence interval, 1.51-4.30; P < 0.01) were observed with MP, which annulled in a secondary analysis with adjustment for the higher dose and metabolite levels | ||
| 520 | |a CONCLUSIONS: Patients treated with MP were relatively higher dosed, which resulted in more dose-dependent side effects and a higher rate of dose reductions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Mercaptopurine |2 NLM | |
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| 650 | 7 | |a Azathioprine |2 NLM | |
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| 700 | 1 | |a Coenen, Marieke J H |e verfasserin |4 aut | |
| 700 | 1 | |a van Marrewijk, Corine J |e verfasserin |4 aut | |
| 700 | 1 | |a Wanten, Geert J A |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Dennis R |e verfasserin |4 aut | |
| 700 | 1 | |a Verbeek, Andre L M |e verfasserin |4 aut | |
| 700 | 1 | |a Klungel, Olaf H |e verfasserin |4 aut | |
| 700 | 1 | |a Hooymans, Piet M |e verfasserin |4 aut | |
| 700 | 1 | |a Guchelaar, Henk-Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Scheffer, Hans |e verfasserin |4 aut | |
| 700 | 1 | |a Derijks, Luc J J |e verfasserin |4 aut | |
| 700 | 1 | |a de Jong, Dirk J |e verfasserin |4 aut | |
| 700 | 0 | |a TOPIC Recruitment Team |e verfasserin |4 aut | |
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