The Effectiveness and Safety of First-Line Thioguanine in Thiopurine-Naïve Inflammatory Bowel Disease Patients

Femke Crouwel; Ahmed B Bayoumy; Chris J J Mulder; Job H C Peters; Paul J Boekema; Luc J J Derijks; Sybrand Y de Boer; Paul C van de Meeberg; Ishfaq Ahmad; Hans J C Buiter; Nanne K de Boer

doi:10.1093/ibd/izad197

The Effectiveness and Safety of First-Line Thioguanine in Thiopurine-Naïve Inflammatory Bowel Disease Patients

Inflamm Bowel Dis. 2023 Sep 2:izad197. doi: 10.1093/ibd/izad197. Online ahead of print.

Authors

Affiliations

¹ Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
² Department of Gastroenterology and Hepatology, Rode Kruis hospital, Beverwijk, the Netherlands.
³ Department of Gastroenterology and Hepatology, Máxima Medical Centre, Veldhoven, the Netherlands.
⁴ Department of Clinical Pharmacy and Pharmacology, Máxima Medical Centre, Veldhoven, the Netherlands.
⁵ Department of Gastroenterology and Hepatology, Slingeland Hospital, Doetinchem, the Netherlands.
⁶ Department of Gastroenterology and Hepatology, Streekziekenhuis Koningin Beatrix, Winterswijk, the Netherlands.
⁷ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

PMID: 37658804
DOI: 10.1093/ibd/izad197

Abstract

Background: Currently thioguanine is solely used as treatment for inflammatory bowel disease after azathioprine and/or mercaptopurine failure. This study aimed to determine the safety, effectiveness, and 12-month drug survival of thioguanine in thiopurine-naïve patients with inflammatory bowel disease.

Methods: A retrospective cohort study was performed in thiopurine-naïve patients with inflammatory bowel disease treated with thioguanine as first thiopurine derivate. Clinical effectiveness was defined as the continuation of thioguanine without the (re)initiation of concurrent biological therapy, systemic corticosteroids, or a surgical intervention. All adverse events were categorized by the Common Terminology Criteria for Adverse Events.

Results: A total of 114 patients (male 39%, Crohn's disease 53%) were included with a median treatment duration of 25 months and a median thioguanine dosage of 20 mg/d. Clinical effectiveness at 12 months was observed in 53% of patients, and 78% of these responding patients remained responsive until the end of follow-up. During the entire follow-up period, 26 patients were primary nonresponders, 8 had a secondary loss of response, and 11 patients were unable to cease therapy with systemic corticosteroids within 6 months and were therefore classified as nonresponders. After 12 months, thioguanine was still used by 86% of patients. Fifty (44%) patients developed adverse events (grade 1 or 2) and 9 (8%) patients ceased therapy due to the occurrence of adverse events. An infection was documented in 3 patients, none of them requiring hospitalization and pancytopenia occurred in 2 other patients. No signs of nodular regenerative hyperplasia or portal hypertension were observed.

Conclusions: At 12 months, first-line thioguanine therapy was clinically effective in 53% of thiopurine-naïve inflammatory bowel disease patients with an acceptable safety profile.

Keywords: clinical effectiveness; inflammatory bowel disease; thioguanine.

Plain language summary

After 12 months, first-line thioguanine therapy was still used by 86% of thiopurine-naïve patients with inflammatory bowel disease and clinically effective in 53%. The safety profile was acceptable and only 8% of patients ceased therapy due to adverse events.