Incidence and pattern of mycophenolate discontinuation associated with abnormal monitoring blood-test results: cohort study using data from the Clinical Practice Research Datalink Aurum

Abstract

Objective To examine the incidence and pattern of mycophenolate discontinuation associated with abnormal monitoring blood-tests. Methods Data from people prescribed mycophenolate for common inflammatory conditions in the Clinical Practice Research Datalink was used. Participants were followed from first mycophenolate prescription. Primary outcome was drug discontinuation with an associated abnormal blood-test result within 60 days. Secondary outcomes were drug discontinuation for any reason, and discontinuations associated with severely abnormal blood-test results within 60 days. Multivariable cox-regression was used to examine factors associated with primary outcome. Results The cohort included 992 participants (68.9% female, mean age 51.95 years, 47.1% with SLE) contributing 1,885 person-years of follow-up. The incidence of mycophenolate discontinuation associated with any (severely) abnormal blood-test results was 153.46 (21.07) per 1000 person-years in the first, and 32.39 (7.91) per 1000 person-years in later years of prescription, respectively. 11.5% (1.7%) patients prescribed mycophenolate discontinued treatment with any (severely) abnormal blood-test results in the first year of prescription. After this period mean 2.6% (0.7%) patients discontinued treatment with any (severely) abnormal blood-test results per year. Increased serum creatinine and cytopenia were more commonly associated with mycophenolate discontinuation than elevated liver enzymes. CKD-stage ≥3 was significantly associated with mycophenolate discontinuation with any blood-test abnormalities (aHR (95%CI) 2.22 (1.47–3.37)). Conclusion Mycophenolate is uncommonly discontinued for blood-test abnormalities, and, even less often discontinued for severe blood-test abnormalities after the first year of prescription. Consideration may be given for less frequent monitoring after one-year of treatment, especially in those without CKD-stage ≥3.

Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review

“…Composite toxicity (treatment discontinuation with cytopenia, acute kidney injury or elevated liver enzymes) There was moderate-quality evidence that epilepsy and blood test abnormalities in the first few months of shared care prescription 34 was associated with composite toxicity in patients prescribed leflunomide and moderate-quality evidence that chronic kidney disease stage 3 35 was associated with composite toxicity in patients prescribed mycophenolate mofetil.…”

Researchers in rheumatology should avoid categorization of continuous predictor variables

“…Epidemiological research can suggest potential risk factors and strategies to prevent, delay or reverse osteoarthritis and other rheumatic diseases. In epidemiological research in osteoarthritis and other rheumatic diseases, it is common practice to categorize a continuous variable that is a predictor of an outcome (the ‘predictor variable’), as evident in studies published in the past two years (2020 to 2022 [ 1 – 7 ]). These studies categorized continuous predictor variables such as: change in weight [ 8 ]; change in body mass index (BMI) [ 2 ]; risk score for mortality [ 3 ]; age [ 3 ]; appendicular lean mass index [ 4 ]; fat mass index [ 4 ]; disease activity score [ 9 ]; years of use of analgesics [ 5 ]; patient global visual analogue scale assessment of disease activity [ 10 ]; the Stanford Health Assessment Questionnaire-Disability Index [ 10 ]; glucocorticoid drug dosage [ 10 ]; swollen joint count [ 6 ]; tender joint count [ 6 ]; and alcohol unit consumption per week [ 7 ].…”

“…In epidemiological research in osteoarthritis and other rheumatic diseases, it is common practice to categorize a continuous variable that is a predictor of an outcome (the ‘predictor variable’), as evident in studies published in the past two years (2020 to 2022 [ 1 – 7 ]). These studies categorized continuous predictor variables such as: change in weight [ 8 ]; change in body mass index (BMI) [ 2 ]; risk score for mortality [ 3 ]; age [ 3 ]; appendicular lean mass index [ 4 ]; fat mass index [ 4 ]; disease activity score [ 9 ]; years of use of analgesics [ 5 ]; patient global visual analogue scale assessment of disease activity [ 10 ]; the Stanford Health Assessment Questionnaire-Disability Index [ 10 ]; glucocorticoid drug dosage [ 10 ]; swollen joint count [ 6 ]; tender joint count [ 6 ]; and alcohol unit consumption per week [ 7 ]. To further exemplify how common the practice of categorization of continuous predictor variables is in rheumatology research, we surveyed articles published in 2021 (the year before commencing this current study) in the journal titled Arthritis Care & Research .…”