OBJECTIVES: The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting. MATERIALS AND METHODS: All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported. RESULTS: Two hundred and fifty three patients were included. Median total follow-up was 32 months (range: 0.2-75 months). At the end of the study, AZA was discontinued in 160 patients (63.2%). The main reason leading to drug withdrawal was the occurrence of AEs (109/160 patients [68.1%]; cumulative incidence among the entire cohort: 43.1%). Overall, the most frequent AEs leading to treatment withdrawal were nausea (31/253 patients, 12.3%) and subjective symptoms, i.e., poorly defined side effects such as fatigue, headache and muscle pain (20/253 patients, 7.9%). Among the 109 AZA-intolerant patients, a switch to 6-mercaptopurine (6-MP) was performed in 44 cases (40.4%). At the end of follow-up, 6-MP was discontinued in 35/44 patients (79.5%), mostly due to AEs (29/35 patients, 82.8%). Azathioprine-induced hepatic and pancreatic toxicity was associated with male gender (p = .01 and p = .03, respectively), and occurrence of nausea with Crohn's disease (p = .04). CONCLUSIONS: Our real-life prospective cohort showed the higher cumulative incidence of thiopurine withdrawal due to AEs reported to date. Switching from AZA to 6-MP was often ineffective.
OBJECTIVES: The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting. MATERIALS AND METHODS: All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported. RESULTS: Two hundred and fifty three patients were included. Median total follow-up was 32 months (range: 0.2-75 months). At the end of the study, AZA was discontinued in 160 patients (63.2%). The main reason leading to drug withdrawal was the occurrence of AEs (109/160 patients [68.1%]; cumulative incidence among the entire cohort: 43.1%). Overall, the most frequent AEs leading to treatment withdrawal were nausea (31/253 patients, 12.3%) and subjective symptoms, i.e., poorly defined side effects such as fatigue, headache and muscle pain (20/253 patients, 7.9%). Among the 109 AZA-intolerant patients, a switch to 6-mercaptopurine (6-MP) was performed in 44 cases (40.4%). At the end of follow-up, 6-MP was discontinued in 35/44 patients (79.5%), mostly due to AEs (29/35 patients, 82.8%). Azathioprine-induced hepatic and pancreatic toxicity was associated with male gender (p = .01 and p = .03, respectively), and occurrence of nausea with Crohn's disease (p = .04). CONCLUSIONS: Our real-life prospective cohort showed the higher cumulative incidence of thiopurine withdrawal due to AEs reported to date. Switching from AZA to 6-MP was often ineffective.
Authors: Pablo A Olivera; Stephane Zuily; Paulo G Kotze; Veronique Regnault; Sameer Al Awadhi; Peter Bossuyt; Richard B Gearry; Subrata Ghosh; Taku Kobayashi; Patrick Lacolley; Edouard Louis; Fernando Magro; Siew C Ng; Alfredo Papa; Tim Raine; Fabio V Teixeira; David T Rubin; Silvio Danese; Laurent Peyrin-Biroulet Journal: Nat Rev Gastroenterol Hepatol Date: 2021-08-27 Impact factor: 46.802
Authors: Remo Panaccione; A Hillary Steinhart; Brian Bressler; Reena Khanna; John K Marshall; Laura Targownik; Waqqas Afif; Alain Bitton; Mark Borgaonkar; Usha Chauhan; Brendan Halloran; Jennifer Jones; Erin Kennedy; Grigorios I Leontiadis; Edward V Loftus; Jonathan Meddings; Paul Moayyedi; Sanjay Murthy; Sophie Plamondon; Greg Rosenfeld; David Schwartz; Cynthia H Seow; Chadwick Williams; Charles N Bernstein Journal: J Can Assoc Gastroenterol Date: 2018-07-10
Authors: Eline L Giraud; Pepijn W A Thomas; Jette A van Lint; Eugene P van Puijenbroek; Tessa E H Römkens; Rachel L West; Maurice G V M Russel; Jeroen M Jansen; Naomi T Jessurun; Frank Hoentjen Journal: Drug Saf Date: 2021-02-04 Impact factor: 5.606
Authors: E H J Savelkoul; M H J Maas; A R Bourgonje; F Crouwel; V B C Biemans; N den Broeder; M G V M Russel; T E H Römkens; N K de Boer; G Dijkstra; F Hoentjen Journal: J Crohns Colitis Date: 2022-09-08 Impact factor: 10.020
Authors: Vince B C Biemans; Edo Savelkoul; Ruben Y Gabriëls; Melek Simsek; Gerard Dijkstra; Marieke J Pierik; Rachel L West; Nanne K H de Boer; Frank Hoentjen Journal: Aliment Pharmacol Ther Date: 2020-04-27 Impact factor: 8.171