Thioguanine is Effective as Maintenance Therapy for Inflammatory Bowel Disease: A Prospective Multicentre Registry Study.
6-thioguanine-nucleotides
Crohn’s disease
Inflammatory bowel disease
azathioprine
mercaptopurine
nodular regenerative hyperplasia
thioguanine
ulcerative colitis
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
16 Jun 2023
16 Jun 2023
Historique:
medline:
19
6
2023
pubmed:
27
1
2023
entrez:
26
1
2023
Statut:
ppublish
Résumé
Thioguanine is a well-tolerated and effective therapy for inflammatory bowel disease [IBD] patients. Prospective effectiveness data are needed to substantiate the role of thioguanine as a maintenance therapy for IBD. IBD patients who previously failed azathioprine or mercaptopurine and initiated thioguanine were prospectively followed for 12 months starting when corticosteroid-free clinical remission was achieved (Harvey-Bradshaw Index [HBI] ≤ 4 or Simple Clinical Colitis Activity Index [SCCAI] ≤ 2). The primary endpoint was corticosteroid-free clinical remission throughout 12 months. Loss of clinical remission was defined as SCCAI > 2 or HBI > 4, need of surgery, escalation of therapy, initiation of corticosteroids or study discontinuation. Additional endpoints were adverse events, drug survival, physician global assessment [PGA] and quality of life [QoL]. Sustained corticosteroid-free clinical remission at 3, 6 or 12 months was observed in 75 [69%], 66 [61%] and 49 [45%] of 108 patients, respectively. Thioguanine was continued in 86 patients [80%] for at least 12 months. Loss of response [55%] included escalation to biologicals in 15%, corticosteroids in 10% and surgery in 3%. According to PGA scores, 82% of patients were still in remission after 12 months and QoL scores remained stable. Adverse events leading to discontinuation were reported in 11%, infections in 10%, myelo- and hepatotoxicity each in 6%, and portal hypertension in 1% of patients. Sustained corticosteroid-free clinical remission over 12 months was achieved in 45% of IBD patients on monotherapy with thioguanine. A drug continuation rate of 80%, together with favourable PGA and QoL scores, underlines the tolerability and effectiveness of thioguanine for IBD.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Thioguanine is a well-tolerated and effective therapy for inflammatory bowel disease [IBD] patients. Prospective effectiveness data are needed to substantiate the role of thioguanine as a maintenance therapy for IBD.
METHODS
METHODS
IBD patients who previously failed azathioprine or mercaptopurine and initiated thioguanine were prospectively followed for 12 months starting when corticosteroid-free clinical remission was achieved (Harvey-Bradshaw Index [HBI] ≤ 4 or Simple Clinical Colitis Activity Index [SCCAI] ≤ 2). The primary endpoint was corticosteroid-free clinical remission throughout 12 months. Loss of clinical remission was defined as SCCAI > 2 or HBI > 4, need of surgery, escalation of therapy, initiation of corticosteroids or study discontinuation. Additional endpoints were adverse events, drug survival, physician global assessment [PGA] and quality of life [QoL].
RESULTS
RESULTS
Sustained corticosteroid-free clinical remission at 3, 6 or 12 months was observed in 75 [69%], 66 [61%] and 49 [45%] of 108 patients, respectively. Thioguanine was continued in 86 patients [80%] for at least 12 months. Loss of response [55%] included escalation to biologicals in 15%, corticosteroids in 10% and surgery in 3%. According to PGA scores, 82% of patients were still in remission after 12 months and QoL scores remained stable. Adverse events leading to discontinuation were reported in 11%, infections in 10%, myelo- and hepatotoxicity each in 6%, and portal hypertension in 1% of patients.
CONCLUSION
CONCLUSIONS
Sustained corticosteroid-free clinical remission over 12 months was achieved in 45% of IBD patients on monotherapy with thioguanine. A drug continuation rate of 80%, together with favourable PGA and QoL scores, underlines the tolerability and effectiveness of thioguanine for IBD.
Identifiants
pubmed: 36702552
pii: 7005319
doi: 10.1093/ecco-jcc/jjad013
pmc: PMC10274302
doi:
Substances chimiques
Thioguanine
FTK8U1GZNX
Azathioprine
MRK240IY2L
Mercaptopurine
E7WED276I5
Immunosuppressive Agents
0
Types de publication
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
933-942Subventions
Organisme : TEVA Nederland B.V.
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.
Références
J Crohns Colitis. 2010 Oct;4(4):484-5
pubmed: 21122549
Inflamm Bowel Dis. 2018 Mar 19;24(4):742-751
pubmed: 29562277
J Crohns Colitis. 2022 Sep 8;16(9):1372-1379
pubmed: 35303065
J Crohns Colitis. 2023 May 3;17(5):738-745
pubmed: 36521000
J Pharm Pharmacol. 1983 Jan;35(1):15-8
pubmed: 6131958
Inflamm Bowel Dis. 2010 Sep;16(9):1541-9
pubmed: 20155846
Gastroenterology. 2003 Aug;125(2):298-303
pubmed: 12891528
BMC Gastroenterol. 2020 Sep 11;20(1):296
pubmed: 32917155
J Gastrointestin Liver Dis. 2020 Dec 13;29(4):637-645
pubmed: 33331335
World J Gastroenterol. 2016 Oct 28;22(40):9012-9021
pubmed: 27833392
Expert Opin Biol Ther. 2016 Oct;16(10):1277-90
pubmed: 27329436
Front Pharmacol. 2021 Apr 14;12:651415
pubmed: 33935763
Ther Drug Monit. 2017 Dec;39(6):584-588
pubmed: 29040228
Clin Transl Gastroenterol. 2016 Jan 07;7:e135
pubmed: 26741065
Inflamm Bowel Dis. 2016 Sep;22(9):2112-20
pubmed: 27482972
Am J Gastroenterol. 1996 Aug;91(8):1571-8
pubmed: 8759664
Aliment Pharmacol Ther. 2022 Sep;56(6):1030-1043
pubmed: 35794735
Gut. 2021 Apr;70(4):677-686
pubmed: 33004550
Am J Gastroenterol. 2007 Nov;102(11):2495-503
pubmed: 17894846
Scand J Gastroenterol. 2019 Jun;54(6):753-760
pubmed: 31203688
PLoS One. 2019 May 24;14(5):e0212157
pubmed: 31125338
Hepatology. 1990 May;11(5):787-97
pubmed: 2189821
Aliment Pharmacol Ther. 2019 Jul;50(1):54-65
pubmed: 31094013
Inflamm Bowel Dis. 2014 Dec;20(12):2239-46
pubmed: 25230165
Expert Opin Drug Metab Toxicol. 2020 Feb;16(2):111-123
pubmed: 32090622