Limited added value of laboratory monitoring in thiopurine maintenance monotherapy in inflammatory bowel disease patients

Joany E. Kreijne, Annemarie C. de Vries, Rozanne C. de Veer, Gerd Bouma, Gerard Dijkstra, Michiel D. Voskuil, Rachel West, Sofia A.W. van Moorsel, Dirk J. de Jong, Nanne K. de Boer, C. Janneke van der Woude*, the initiative on Crohn and Colitis (ICC)

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: To timely detect myelotoxicity and hepatotoxicity, laboratory monitoring at 3-month intervals is advised throughout thiopurine maintenance treatment for IBD. However, reported incidence rates of myelotoxicity and hepatotoxicity in maintenance treatment are low. Aim: To assess incidence rates and clinical consequences of myelotoxicity and hepatotoxicity in thiopurine maintenance therapy after at least 1 year of thiopurine treatment. Methods: Retrospective analysis of therapy adjustment for laboratory toxicity in adult IBD patients after 12 consecutive months of azathioprine (AZA) or mercaptopurine monotherapy (ie baseline) between 2000 and 2016. Incidence rates of laboratory toxicity (ie myelotoxicity [leucocyte count <4.0 × 10e9/L, and/or platelet count <150 × 10e9/L] and/or hepatotoxicity (gamma-glutamyltransferase [GGT], alkaline phosphatase [AP], ALT and/or AST above ULN, excluding isolated increased AST/AP]) and associated diagnostic procedures and complications were assessed. Results: In total, 12.391 laboratory assessments were performed on 1132 patients (56% female, AZA 74%) during 3.3 years of median follow-up. Median monitoring frequency was 3.1 assessments/treatment year. Only 83/12.391 (0.7%) assessments resulted in therapy adjustment, dose reduction in 46 patients, cessation in 28 and allopurinol initiation in nine; risk of therapy adjustment was 1.9% per treatment year. Incidence rates of myelotoxicity were 7.1% (5.1% mild/1.8% moderate/0.1% severe) and hepatotoxicity 5.1% (3.8% mild/1.1% moderate/0.2% severe) per treatment year. Treatment-related complications with concurrent laboratory toxicity occurred in 12 patients (1.1%) and would not have been prevented by monitoring. Conclusion: Severe laboratory toxicity is uncommon after 1 year of thiopurine monotherapy at 4-month monitoring intervals. Therapy adjustments are rare after detection of laboratory toxicity. After 1 year of thiopurine monotherapy, laboratory monitoring may be lowered to less than a 4-month interval.

Original languageEnglish
Number of pages12
JournalAlimentary Pharmacology and Therapeutics
Volume51
Issue number12
DOIs
Publication statusAccepted/In press - 1 Jan 2020

Cite this

Kreijne, J. E., de Vries, A. C., de Veer, R. C., Bouma, G., Dijkstra, G., Voskuil, M. D., ... the initiative on Crohn and Colitis (ICC) (Accepted/In press). Limited added value of laboratory monitoring in thiopurine maintenance monotherapy in inflammatory bowel disease patients. Alimentary Pharmacology and Therapeutics, 51(12). https://doi.org/10.1111/apt.15734