Persistently normal blood tests in patients taking methotrexate for RA or azathioprine for IBD: 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

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Background: Disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate and azathioprine, are commonly used for 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 RA patients prescribed methotrexate and IBD patients prescribed azathioprine.

Design and setting: Two-year retrospective cohort study using pseudonymised primary care/laboratory data in Hampshire.

Method: RA and IBD patients were identified with associated methotrexate (RA) and azathioprine (IBD) prescriptions. NICE-recommended tests and thresholds were applied and persistent normality defined as a) no abnormalities of any tests, and b) individually for alanine aminotransferase (ALT), estimated glomerular filtration rate (eGFR), white blood count (WBC), and neutrophils. Logistic regression was used to identify associations with test normality.

Results: Of 702,265 adults, 7102 had RA and 8597 had IBD. 3001 (42.2%) RA patients were prescribed methotrexate and 1162 (13.5%) IBD patients prescribed azathioprine. Persistently normal tests occurred in 1585 (52.8%) of the RA/methotrexate and 657 (56.5%) of the IBD/azathioprine populations. In RA/methotrexate patients 585 (19.5%) had eGFR, 219 (7.3%) ALT, 217 (7.2%) WBC, and 202 (6.7%) neutrophil abnormalities. In IBD/azathioprine patients 138 (4.6%) had WBC, 88 (2.9%) eGFR, 72 (2.4%) ALT and 65 (2.2%) neutrophil abnormalities. Those least likely to have persistent test normality were older and/or had comorbidities.

Conclusions: Persistent test normality is common in monitoring these DMARDs in primary care, with few hepatic or haematological abnormalities. More stratified monitoring approaches should be explored.
Original languageEnglish
Pages (from-to)e528-e537
JournalBritish Journal of General Practice (BJGP)
Issue number720
Early online date24 Jan 2022
Publication statusPublished - 1 Jul 2022


  • clinical (physical)
  • renal medicine
  • research methods
  • epidemiology


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