6-Thioguanine therapy in Crohn's disease-Observational data in Swedish patients
(2009) In Digestive and Liver Disease 41(3). p.194-200- Abstract
- Background and aims. Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety. Methods. We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohn's disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n = 18) or resistance (It = 5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times. Results.... (More)
- Background and aims. Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety. Methods. We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohn's disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n = 18) or resistance (It = 5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times. Results. Patients were treated with a median daily dose of 40 mg 6-TG (range 20-60) for 259 (15-2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4-26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation (n=10) after 85 (15-451) days or dose reduction (n=6) after 78 (10-853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance (p=0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure (n=5) or safety concerns (n=3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99-2488) vs. 551 (392-1574) pmol/8 x 10(8) RBC; p=0.80. Conclusions. In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered. (C) 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1404940
- author
- Almer, S. H. C. ; Hjortswang, H. and Hindorf, Ulf LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Thiopurine drugs, 6-thioguanine, Inflammatory bowel disease, toxicity, Drug
- in
- Digestive and Liver Disease
- volume
- 41
- issue
- 3
- pages
- 194 - 200
- publisher
- Elsevier
- external identifiers
-
- wos:000264228700003
- scopus:60649106530
- ISSN
- 1590-8658
- DOI
- 10.1016/j.dld.2008.07.314
- language
- English
- LU publication?
- yes
- id
- 11902a6e-7a1d-4f32-adae-be88ae82149f (old id 1404940)
- date added to LUP
- 2016-04-01 11:33:41
- date last changed
- 2024-10-08 01:53:00
@article{11902a6e-7a1d-4f32-adae-be88ae82149f,
abstract = {{Background and aims. Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety. Methods. We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohn's disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n = 18) or resistance (It = 5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times. Results. Patients were treated with a median daily dose of 40 mg 6-TG (range 20-60) for 259 (15-2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4-26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation (n=10) after 85 (15-451) days or dose reduction (n=6) after 78 (10-853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance (p=0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure (n=5) or safety concerns (n=3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99-2488) vs. 551 (392-1574) pmol/8 x 10(8) RBC; p=0.80. Conclusions. In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered. (C) 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.}},
author = {{Almer, S. H. C. and Hjortswang, H. and Hindorf, Ulf}},
issn = {{1590-8658}},
keywords = {{Thiopurine drugs; 6-thioguanine; Inflammatory bowel disease; toxicity; Drug}},
language = {{eng}},
number = {{3}},
pages = {{194--200}},
publisher = {{Elsevier}},
series = {{Digestive and Liver Disease}},
title = {{6-Thioguanine therapy in Crohn's disease-Observational data in Swedish patients}},
url = {{http://dx.doi.org/10.1016/j.dld.2008.07.314}},
doi = {{10.1016/j.dld.2008.07.314}},
volume = {{41}},
year = {{2009}},
}