Few Hepatic Events for Rheumatoid Arthritis, IBD Patients Treated with DMARDs


Less than 5% of patients with IBD treated with azathioprine had white blood count, eGFR, ALT, and neutrophil abnormalities.

Simon D. Fraser, MD

Simon D. Fraser, MD

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) are often treated with disease-modifying anti-rheumatic drugs (DMARDs), but whether these drugs effect blood or kidney function is underexplored.

A team, led by Simon D. Fraser, MD, School of Primary Care, Population Sciences and Medical Education, University of Southampton, identified the frequency and associations of persistently normal blood tests in rheumatoid arthritis patients prescribed methotrexate and patients with IBD prescribed azathioprine.

Disease-modifying anti-rheumatic drugs can be used for both rheumatoid arthritis and IBD. This class of drugs can include methotrexate and azathioprine.

Blood test safety monitoring is often undertaken in primary care, with normal blood results commonly found.

The Study

In the two-year retrospective cohort study, the investigators used pseudonymized primary care and laboratory data in Hampshire. The investigators identified patients with either rheumatoid arthritis and IBD with associated methotrexate and azathioprine prescriptions.

There was a total of 702,265 adults, identified, 7102 of which had rheumatoid arthritis and 8597 of which had IBD.

They then applied NICE-recommended tests and thresholds and defin ed persistent normality as no abnormalities of any tests and individually for alanine aminotransferase (ALT), estimated glomerular filtration rate (eGFR), white blood count (WBC), and neutrophils.

The team also used logistic regression to identify the associations with test normality. For prescriptions, 42.2% (n = 3001) of patients with rheumatoid arthritis were prescribed methotrexate and 13.5% (n = 1162) of patients with IBD were prescribed azathioprine.

Blood Test Findings

There were persistently normal tests identified in 52.8% (n = 1585) of the rheumatoid arithritis/methotrexate group and 56.5% (n = 657) of the IBD/azathioprine cohort.

In addition, 19.5% (n = 585) the methotrexate patients had eGFR abnormalities, 7.3% (n = 219) had ALT abnormalities, 72.% (n = 217) had white blood count abnormalities, and 6.7% (n = 202) had neutrophil abnormalities.

For the azathioprine group, 4.6% (n = 138) had white blood count abnormalities, 2.9% (n = 88) had eGFR abnormalities, 2.4% (n = 72) had ALT abnormalities, and 2.2% (n = 65) had neutrophil abnormalities.

In addition, individuals least likely to have persistent test normality were generally older and/or had comorbidities.

“Persistent test normality is common in monitoring these DMARDs in primary care, with few hepatic or haematological abnormalities,” the authors wrote. “More stratified monitoring approaches should be explored.”

Chronic Kidney Disease

In a 2020 study, investigators found IBD is associatioed with the development of chronic kidney disease in patients between 16-77 years.

However, as patients age increased, the adjusted hazard ratio for chronic kidney disease decreased monotonically significantly.

The adjusted hazard ratio decreased from 7.88 (95% CI, 2.56—24.19) at age 16 to 1.13 (95% CI, 1.01–1.25) at age 77.

Using the longitudinal analysis, the investigators discovered that exposure to 5-ASAs or methotrexate was not linked to changes in eGFR. On the other hand, azathioprine was associated with a slightly higher eGFR (.32 mL/min/1.73m2; 95% CI, 0.16-0.48).

The study, “Identifying individuals with persistently normal safety monitoring blood tests whilst taking methotrexate for rheumatoid arthritis or azathioprine for inflammatory bowel disease: a retrospective cohort study,” was published online in the British Journal of General Practice.

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