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

Abstract

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.

Saving the planet with reduced routine DMARD blood monitoring frequency

“…The recent paper from Nakafero and colleagues1 adds to a growing evidence base showing that patients stable on low dose methotrexate in the long term are unlikely to develop significant blood abnormalities 23. In our own cohort of patients stable on methotrexate we found that reduced monitoring frequency as a result of the pandemic did not lead to more abnormal results 4.…”

Psoriasis/Psoriatic Arthritis Patients’ Long-term Treatment Patterns and Adherence to Systemic Treatments Monitoring Recommendations

“…During long-term therapy, 50% of patients did not undergo annual monitoring. Other studies from different regions of the world have suggested suboptimal monitoring to be common, with rates as low as 42% reported in a German study ( 32 ) of patients initiating MTX, and <65% in a UK cohort ( 33 ) from general practitioners. A French study reported that approximately 65% of patients starting MTX underwent pre-initiation monitoring and <50% during follow-up and that more frequent monitoring led to earlier discontinuation of MTX therapy ( 34 ).…”

Risk stratified monitoring for methotrexate toxicity in immune mediated inflammatory diseases: prognostic model development and validation using primary care data from the UK

“…Lengthening the time between monitoring blood tests would save patients’ and health professionals’ time, minimise discomfort from unnecessary venepunctures, and conserve healthcare resources, because patients with well controlled immune mediated inflammatory diseases undergo quarterly monitoring blood tests at their GP’s surgery or at hospital or community phlebotomy services and are only followed-up in specialist clinics annually. Patients taking methotrexate are usually adherent to monitoring recommendations, 12 and our model, if implemented, should reduce the volume of monitoring blood tests. It is important that the results of this study are not used to risk stratify monitoring in patients who have recently started methotrexate treatment because we did not use data on such patients in our study.…”

“… 6 7 8 Methotrexate use has increased in the era of biologics, with only a few patients (about 3%) with rheumatoid arthritis or with psoriasis with or without arthritis prescribed biologics in European countries. 9 10 11 12 …”

“…[6][7][8] Methotrexate use has increased in the era of biologics, with only a few patients (about 3%) with rheumatoid arthritis or with psoriasis with or without arthritis prescribed biologics in European countries. [9][10][11][12] Although effective and well tolerated, methotrexate can cause cytopenia, raised liver enzyme levels, and acute kidney injury, mostly during the first few months of treatment. 13 14 Concern about these side effects has led to the recommendation to perform blood tests every two to four weeks to monitor patients for full blood count, liver function, and urea electrolytes and creatinine during the initial few months of treatment, followed thereafter by tests every three months for everyone.…”