Long-Term Routine Laboratory Toxicity Monitoring of Immunomodulatory Drugs in Rheumatoid Arthritis

Background: Scarcity of data on the value of long-term routine laboratory toxicity monitoring (lt-RLTM) during disease-modifying antirheumatic drug (DMARD) use results in frequent monitoring in clinical practice. Objective: To determine the cumulative incidence of abnormal and very abnormal laboratory monitoring results among patients with rheumatoid arthritis (RA) and to characterize the clinical context for the incidence of new very abnormal results. Design: Retrospective cohort study. Setting: The Netherlands, July 2008 to April 2020. Patients: Patients with RA undergoing lt-RLTM after at least 6 months of DMARD use. Measurements: Cumulative probabilities of abnormal and very abnormal results were calculated for alanine aminotransferase (>100 and >300 U/L), estimated glomerular filtration rate (eGFR; <60 and <45 mL/ min/1.73 m²), hemoglobin (Hb; <7.5 mmol/L [females] or <8 mmol/L [males] and <6 mmol/L), leukocyte count (<3.5 and <2.0 × 10⁹/L), and platelet count (<140 and <100 × 10⁹/L). Chart review for newly occurring very abnormal results was performed for clinical context. Results: 4774 patients underwent 59555 lt-RLTM test sets over 18383 patient-years. The cumulative probabilities of very abnormal laboratory results for the 5 tests varied from 0.2% (leukocyte count) to 6.6% (eGFR) at 2 years and from 0.3% (leukocyte count) to 11% (eGFR) at 5 years. New very abnormal results (n = 449) mostly occurred after a dose increase (6.5%), were often already known or suspected (47.7%), were considered to be unrelated to DMARD use (24.1%), or did not lead to action (35.8%). The incidence of less serious abnormal results was higher, as high as 39% for eGFR less than 60 mL/min/1.73 m² and 61% for Hb level below 7.5 mmol/L for females or below 8 mmol/L for males. Limitation: The possibility that regular monitoring contributed to lack of serious adverse outcomes cannot be excluded. Conclusion: Routine laboratory monitoring after 6 months of DMARD use revealed that most very abnormal laboratory results were already clinically anticipated and often occurred after dose escalation, although the cumulative incidence of some less serious abnormal results was quite high. Strategies for lt-RLTM warrant reconsideration. Primary Funding Source: None.