@article{90d00b4328a34345926f8ea2f39219f1,
title = "A comparative analysis of tioguanine versus low-dose thiopurines combined with allopurinol in inflammatory bowel disease patients",
abstract = "Background Both tioguanine and low-dose thiopurines combined with allopurinol (LDTA) can be considered for the treatment of inflammatory bowel disease (IBD) when conventional thiopurines fail due to adverse events.Aim To compare the safety of tioguanine and LDTA in IBD patients.Methods Inflammatory bowel disease patients who failed conventional thiopurines due to adverse events and initiated LDTA in standard care were identified in the prospective ICC Registry. IBD patients who failed conventional thiopurines due to adverse events and initiated tioguanine were enrolled in three university hospitals. Patients on concomitant biologicals were excluded. The primary outcome was discontinuation of therapy due to adverse events. Secondary outcomes included: safety outcomes and surgery-, biological- and corticosteroid-free clinical remission (physician global assessment = 0) after 104 weeks. Both multiple logistic regression and propensity score matching were used to correct for confounders.Results In total, 182 IBD patients treated with tioguanine (n = 94) or LDTA (n = 88) were included with a median follow-up of 104 weeks (IQR 91-104). Of these, 19% (tioguanine: 20%, LDTA: 18%) of patients discontinued therapy due to adverse events. After adjusting for confounders, there were no differences in terms of discontinuation rate due to adverse events (OR 0.50, 95% CI 0.15-1.68, P = 0.26), adverse events (OR 0.89, 95% CI 0.44-1.81, P = 0.75), infections (OR 1.05, 95% CI 0.40-2.73, P = 0.93), hospitalisations (OR 2.00, 95% CI 0.64-6.23, P = 0.23) or clinical remission (OR 0.74, 95%CI 0.33-1.68, P = 0.48). All results are comparable with the propensity score matched cohort.Conclusion Nineteen percent of IBD patients with prior failure to conventional thiopurines due to adverse events discontinued therapy with tioguanine or LDTA due to adverse events. Either therapy may be considered before escalating to biological therapy.",
keywords = "adverse events, azathioprine, combination therapy, crohns-disease, efficacy, infliximab, intensification, prevalence, safety, thioguanine, CROHNS-DISEASE, EFFICACY, SAFETY, COMBINATION THERAPY, AZATHIOPRINE, PREVALENCE, INTENSIFICATION, THIOGUANINE, INFLIXIMAB, ADVERSE EVENTS",
author = "V.B.C. Biemans and E. Savelkoul and R.Y. Gabriels and M. Simsek and G. Dijkstra and M.J. Pierik and R.L. West and {de Boer}, N.K.H. and F. Hoentjen and {Dutch Initiative on Crohn and Colitis (ICC)}",
note = "Funding Information: No funding has been received for this specific study. Data have been generated as part of routine work of the participating organisations. Declaration of personal interests: VBC Biemans, E. Savelkoul, RY Gabri?ls have no conflicts of interest to declare. G. Dijkstra unrestricted research grants from Abbvie and Takeda. Advisory boards for Mundipharma and Pharmacosmos. Received speakers fees from Abbvie, Takeda and Janssen Pharmaceuticals. M. Simsek has received an unrestricted research grant from Teva Pharma BV. NKH de Boer has served as a speaker for AbbVie, Takeda and MSD. He has served as consultant and principal investigator for Takeda and TEVA Pharma BV He has received (unrestricted) research grants from Dr Falk, TEVA Pharma BV, and Takeda. MJ Pierik has served on advisory boards, or as speaker or consultant for?Abbvie, Janssen-Cilag, MSD, Takeda, Ferring, Dr Falk, and Sandoz and has received unrestricted grants from, Janssen-Cilag, Abbvie and Takeda outside the submitted work. RL West has served as a speaker for Takeda. She has served as principal investigator for Abbvie, Ferring and Janssen. She has received (unrestricted) research grants from Janssen and Abbvie. F. Hoentjen has served on advisory boards, or as speaker or consultant for?Abbvie, Celgene, Janssen-Cilag, MSD, Takeda, Celltrion, Teva, Sandoz and Dr Falk, and has received unrestricted grants from Dr Falk, Janssen-Cilag, Abbvie. Funding Information: VBC Biemans, E. Savelkoul, RY Gabri{\"e}ls have no conflicts of interest to declare. G. Dijkstra unrestricted research grants from Abbvie and Takeda. Advisory boards for Mundipharma and Pharmacosmos. Received speakers fees from Abbvie, Takeda and Janssen Pharmaceuticals. M. Simsek has received an unrestricted research grant from Teva Pharma BV. NKH de Boer has served as a speaker for AbbVie, Takeda and MSD. He has served as consultant and principal investigator for Takeda and TEVA Pharma BV He has received (unrestricted) research grants from Dr Falk, TEVA Pharma BV, and Takeda. MJ Pierik has served on advisory boards, or as speaker or consultant for Abbvie, Janssen‐Cilag, MSD, Takeda, Ferring, Dr Falk, and Sandoz and has received unrestricted grants from, Janssen‐Cilag, Abbvie and Takeda outside the submitted work. RL West has served as a speaker for Takeda. She has served as principal investigator for Abbvie, Ferring and Janssen. She has received (unrestricted) research grants from Janssen and Abbvie. F. Hoentjen has served on advisory boards, or as speaker or consultant for Abbvie, Celgene, Janssen‐Cilag, MSD, Takeda, Celltrion, Teva, Sandoz and Dr Falk, and has received unrestricted grants from Dr Falk, Janssen‐Cilag, Abbvie. Declaration of personal interests: Publisher Copyright: {\textcopyright} 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd",
year = "2020",
month = jun,
day = "1",
doi = "10.1111/apt.15730",
language = "English",
volume = "51",
pages = "1076--1086",
journal = "Alimentary Pharmacology & Therapeutics",
issn = "0269-2813",
publisher = "John Wiley & Sons Inc.",
number = "11",
}