Persistently normal blood tests in patients taking methotrexate for RA or azathioprine for IBD: a retrospective cohort study: a retrospective cohort study

Simon D. Fraser, Sharon X. Lin, Mathew Stammers, David Culliford, Kinda Ibrahim, Ravina Barrett, Clare Howard, Ruth Johnson, Nicola Barnes, James Batchelor, Christopher Holroyd, Jo Adams, Adam Rischin, Paul Roderick, Paul Rutter, Christopher Edwards

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate and azathioprine, are commonly used to treat rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Blood-test safety monitoring is mainly undertaken in primary care. Normal blood results are common. AIM: To determine the frequency and associations of persistently normal blood tests in patients with RA prescribed methotrexate, and patients with IBD prescribed azathioprine. DESIGN AND SETTING: Two-year retrospective study of a cohort taken from an electronic pseudonymised primary care/laboratory database covering >1.4 million patients across Hampshire, UK. METHOD: Patients with RA and IBD, and associated methotrexate and azathioprine prescriptions, respectively, were identified. Tests and test thresholds recommended by the National Institute for Health and Care Excellence were applied. Persistent normality was defined as no abnormalities of any tests nor alanine aminotransferase (ALT), white blood count (WBC), neutrophils, and estimated glomerular filtration rate (eGFR) individually. Logistic regression was used to identify associations with test normality. RESULTS: Of 702 265 adults, 7102 had RA and 8597 had IBD. In total, 3001 (42.3%) patients with RA were prescribed methotrexate and 1162 (13.5%) patients with IBD were prescribed azathioprine; persistently normal tests occurred in 1585 (52.8%) and 657 (56.5%) of the populations, respectively. In patients with RA on methotrexate, 585 (19.5%) had eGFR, 219 (7.3%) ALT, 217 (7.2%) WBC, and 202 (6.7%) neutrophil abnormalities. In patients with IBD on azathioprine, 138 (11.9%) had WBC, 88 (7.6%) eGFR, 72 (6.2%) ALT, and 65 (5.6%) neutrophil abnormalities. Those least likely to have persistent test normality were older and/or had comorbidities. CONCLUSION: Persistent test normality is common when monitoring these DMARDs, with few hepatic or haematological abnormalities. More stratified monitoring approaches should be explored.

Original languageEnglish
Article number BJGP.2021.0595
Pages (from-to)e528-e537
Number of pages24
JournalBritish Journal of General Practice
Issue number720
Publication statusPublished - 24 Jan 2022

Bibliographical note

Funding Information:
This report is independent research funded/ supported by the National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) Wessex. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Publisher Copyright:
© 2022 Royal College of General Practitioners. All rights reserved.


  • Clinical (physical)
  • Renal medicine
  • Research methods
  • Epidemiology


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