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Inflamm Bowel Dis. 2018 Jun 8;24(7):1558-1565. doi: 10.1093/ibd/izy047.

Methotrexate and Thioguanine Rescue Therapy for Conventional Thiopurine Failing Ulcerative Colitis Patients: A Multi-center Database Study on Tolerability and Effectiveness.

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Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam.
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam.
Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam.
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden.
Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht.
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen.
Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen.
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht.
Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical Center, Heerlen-Sittard-Geleen.



Patients with active ulcerative colitis (UC) failing conventional therapies are in need of rescue strategies. Due to the fact that accepted step-up therapy with biologicals is expensive and sometimes unavailable, alternative therapies are warranted. Methotrexate (MTX) and thioguanine (TG) have both been suggested as alternative maintenance strategies in conventional thiopurine failing UC patients. In this multicenter database study, we compared safety and effectiveness (drug-survival) of MTX and TG in UC patients.


We collected data from the Parelsnoer database, a prospective Dutch national database consisting of inflammatory bowel disease patients from all university hospitals in The Netherlands. Additional data were collected from detailed chart review.


In total, 99 UC patients were included, of which 48 used TG, 43 used MTX, and 8 patients had a history of both TG and MTX use. In 12% of the patients, biological therapy had failed. Roughly 70% of the patients in both groups were able to continue therapy for over 1 year. Adverse events were noted in 33% of all the patients and were mainly elevated liver enzymes or gastrointestinal complaints. Twenty-eight patients (28%) continued therapy (15 TG, 13 MTX) without the need of escalation therapy (eg, corticosteroids, biologicals, or surgery). Drug survival curves of both drugs were comparable, just as the number of patients with sustained clinical benefit of therapy (P > 0.05).


Both MTX and TG may be used and maintained as rescue therapy with sustained clinical benefit in one-third of the UC patients failing conventional therapies.

[Indexed for MEDLINE]

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