Low-dose thioguanine guided by therapeutic drug monitoring is a safe and effective alternative in inflammatory bowel disease patients intolerant to conventional thiopurines.
inflammatory bowel disease
therapeutic drug monitoring
thioguanine
thiopurine intolerance
Journal
Internal medicine journal
ISSN: 1445-5994
Titre abrégé: Intern Med J
Pays: Australia
ID NLM: 101092952
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
18
11
2021
received:
12
05
2021
accepted:
25
11
2021
medline:
17
5
2023
pubmed:
8
12
2021
entrez:
7
12
2021
Statut:
ppublish
Résumé
Thioguanine is an alternative thiopurine for inflammatory bowel disease (IBD) patients. To evaluate the short-term efficacy and safety of low-dose therapeutic drug-monitored (TDM) thioguanine. A retrospective evaluation of IBD patients intolerant to conventional thiopurines started on thioguanine from 2017 to 2019 with dosing guided by TDM was conducted. Clinical response was defined for ulcerative colitis (UC) as a reduction of partial Mayo score ≥3 with reduction in rectal bleeding score of at least 1 and a final rectal bleeding subscore of 0-1 at Week 12 of therapy. Crohn disease (CD) response was defined as a reduction of Harvey-Bradshaw index ≥3 (HBI) at Week 12 of therapy. Remission was defined in UC as partial Mayo score of <2 and in CD as HBI score of <5. Forty-six patients were included in the study. The median thioguanine dose was 20 mg/day (standard deviation 7.3; range: 10-40 mg/day) with a median 6-thioguanine nucleotide level of 577 pmol/8 × 108 (interquartile range (IQR) IQR 378.5-878.75) for CD and 677.5 pmol/8 × 108 (IQR 523.25-842.25) for UC. The overall clinical response rate was 62% (13/21), intention to treat (ITT). Maintenance of remission was 76% (19/25, ITT). Thirty-seven percent (17/46) of patients experienced an adverse effect. No early cases of nodular regenerative hyperplasia (NRH) were seen. Thioguanine was tolerated well in 63% of patients. A clinical response was seen in 62% of patients, and maintenance of remission was high at 76%. No cases of early NRH were seen. Longer-term follow up is required to ensure safety and to assess durability of response.
Sections du résumé
BACKGROUND
Thioguanine is an alternative thiopurine for inflammatory bowel disease (IBD) patients.
AIMS
To evaluate the short-term efficacy and safety of low-dose therapeutic drug-monitored (TDM) thioguanine.
METHODS
A retrospective evaluation of IBD patients intolerant to conventional thiopurines started on thioguanine from 2017 to 2019 with dosing guided by TDM was conducted. Clinical response was defined for ulcerative colitis (UC) as a reduction of partial Mayo score ≥3 with reduction in rectal bleeding score of at least 1 and a final rectal bleeding subscore of 0-1 at Week 12 of therapy. Crohn disease (CD) response was defined as a reduction of Harvey-Bradshaw index ≥3 (HBI) at Week 12 of therapy. Remission was defined in UC as partial Mayo score of <2 and in CD as HBI score of <5.
RESULTS
Forty-six patients were included in the study. The median thioguanine dose was 20 mg/day (standard deviation 7.3; range: 10-40 mg/day) with a median 6-thioguanine nucleotide level of 577 pmol/8 × 108 (interquartile range (IQR) IQR 378.5-878.75) for CD and 677.5 pmol/8 × 108 (IQR 523.25-842.25) for UC. The overall clinical response rate was 62% (13/21), intention to treat (ITT). Maintenance of remission was 76% (19/25, ITT). Thirty-seven percent (17/46) of patients experienced an adverse effect. No early cases of nodular regenerative hyperplasia (NRH) were seen.
CONCLUSION
Thioguanine was tolerated well in 63% of patients. A clinical response was seen in 62% of patients, and maintenance of remission was high at 76%. No cases of early NRH were seen. Longer-term follow up is required to ensure safety and to assess durability of response.
Substances chimiques
Thioguanine
FTK8U1GZNX
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
559-567Informations de copyright
© 2021 Royal Australasian College of Physicians.
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