Utility of long-term routine laboratory toxicity monitoring of immunomodulatory drugs in rheumatoid arthritis

1. In this retrospective cohort study involving patients with rheumatoid arthritis on disease-modifying antirheumatic drugs, long-term routine laboratory toxicity monitoring (lt-RLTM) revealed very abnormal results in less than one percent of all completed tests.

2. Most very abnormal laboratory results were already clinically anticipated and were most often due to renal and urinary disorders unrelated to DMARD use.

Evidence Rating Level: 2 (Good)

Study Rundown: Patients with rheumatoid arthritis (RA) using disease-modifying antirheumatic drugs (DMARDs) are recommended to undergo long term routine laboratory toxicity monitoring (lt-RLTM), involving intensive monitoring in the first 6 months followed by less frequent monitoring for the duration of DMARD use. Current knowledge on the optimal frequency of lt-RLTM is lacking, as reflected in the inconsistency across many existing guidelines. Some studies have also suggested that reduced frequencies not only do not increase patient harm but instead could reduce health care burden and expenses. This study aimed to determine the cumulative probability of and clinical context behind abnormal and very abnormal lt-RLTM test results among patients with RA using DMARDs. Among nearly three hundred thousand lt-RLTM tests, over five percent of results were abnormal and less than one percent were very abnormal. Among patients with new very abnormal results, the median age was high, and a large proportion of patients had high pretest probabilities for abnormal laboratory results. New very abnormal results were most often due to renal and urinary disorders unrelated to DMARD use, including chronic kidney disease, acute kidney injury, and kidney stones. The generalizability of this study is limited by an inability to attribute a lack of serious adverse clinical outcomes to inappropriate testing, as well as challenges conducting subgroup analyses based on each treatment or treatment combination. Nevertheless, this study suggests that current lt-RLTM guidelines may result in unnecessary testing for some laboratory parameters.

Click to read this study in AIM

Relevant Reading: Saving the planet with reduced routine DMARD blood monitoring frequency

In-Depth [retrospective cohort]: This retrospective cohort study aimed to evaluate the cumulative probability of abnormal and very abnormal lt-RLTM test results among patients with RA using DMARDs as well as the clinical context behind very abnormal results. A total of 4774 patients were included in this study, with total follow-up of 18,383 patient-years and yielding 8129 patient-DMARD exposure periods. A total of 297,775 lt-RLTM tests were conducted, grouped into 59,555 sets of 5 tests each, with a mean of 12 test sets per patient and 3.2 test sets per patient-year. Abnormal results were most common for estimated glomerular filtration rate (eGFR; 5.3%) and hemoglobin (12%), while very abnormal results were most common for eGFR (1.3%). Among all lt-RLTM tests, 17,343 (5.8%) results were abnormal and 2064 (0.69%) results were very abnormal. Very abnormal results occurred in 492 unique patients, of whom 449 received new results. The cumulative probabilities of abnormal results for the 5 lt-RLTM tests ranged from 4.4% to 47% at 2 years and from 7.5% to 61% at 5 years. The cumulative probabilities of very abnormal results for the 5 tests varied between 0.2% and 6.6% at 2 years and between 0.3% and 11% at 5 years. Among the 449 patients with new very abnormal results, the median age was 73 years (interquartile range [IQR], 65.9 to 79.7), 69.9% (n = 314) were female, and a large proportion had high pretest probability for abnormal results. Test results were deemed unrelated to DMARDs in 116 (24.1%) of participants. New very abnormal causes were mainly due to renal and urinary disorders unrelated to DMARDs, including chronic kidney disease, acute kidney injury, and kidney stones. Overall, this study suggests that lt-RLTM reveals a low proportion of tests as abnormal or very abnormal, and that new very abnormal results may often be unrelated to DMARDs.

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