Thiopurines vs methotrexate: Comparing tolerability and discontinuation rates in the treatment of inflammatory bowel disease

Abhinav Vasudevan, Nina Parthasarathy, Danny Con, Steven Nicolaides, Ross Apostolov, Ayushi Chauhan, Maria Bishara, Raphael P. Luber, Neetima Joshi, Anna Wan, James A. Rickard, Tony Long, Declan Connoley, Miles P. Sparrow, Peter R. Gibson, Daniel R. van Langenberg

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)


Background: There are safety concerns regarding immunomodulators (thiopurines and methotrexate) for treatment of inflammatory bowel disease (IBD). Aim: To compare the long-term tolerability, and persistence of thiopurine and methotrexate therapy in IBD. Methods: A retrospective cohort study was performed at two hospitals between 1 January 2004 and 31 December 2016 for patients commenced on thiopurines or methotrexate for IBD. Treatment discontinuation rates, intolerances and disease activity were obtained from medical records. Results: There were 782 patients commenced on immunomodulator therapy; 244 (31%) on methotrexate with folate (67% subcutaneous therapy) and 538 (69%) on thiopurine (73% azathioprine). Median follow-up was 42 vs 47 months (P = 0.09). In patients on thiopurines, median 6-TGN was 298 pmol/8 x 108 RBCs, while the median dose of methotrexate was 25 mg weekly. Methotrexate recipients had a higher rate of prior immunomodulator intolerance, were typically older and had a longer disease duration (54% vs 3%, median 43 vs 36 years, 6 vs 5 years, respectively, each P < 0.05). Overall, 208 (27%) discontinued therapy due to adverse events, (40% on methotrexate vs 19% on thiopurines, P < 0.001), including nausea (18% vs 4%), fatigue (7% vs 2%) and hepatotoxicity (8% vs 2%, each P < 0.001). Hospitalisations from adverse events (0.8% vs 0.9%) and serious infections (9% vs 12%), and deaths (1% vs 0%) were comparable between groups (all P > 0.05). Discontinuation due to adverse events occurred later in patients on methotrexate than on thiopurines (median 7 vs 5 months, P = 0.08). Conclusion: Discontinuation of methotrexate occurred at rates twice that of dose-optimised thiopurine therapy.

Original languageEnglish
Pages (from-to)1174-1184
Number of pages11
JournalAlimentary Pharmacology & Therapeutics
Issue number7
Publication statusPublished - Oct 2020


  • azathioprine
  • immunomodulator
  • intolerance
  • mercaptopurine
  • side effects

Cite this