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What is the incidence of methotrexate or leflunomide discontinuation related to cytopenia, liver enzyme elevation or kidney function decline?

Nakafero, Georgina; Grainge, Matthew J; Card, Tim; Mallen, Christian D; Zhang, Weiya; Doherty, Michael; Taal, Maarten W; Aithal, Guruprasad P; Abhishek, Abhishek

What is the incidence of methotrexate or leflunomide discontinuation related to cytopenia, liver enzyme elevation or kidney function decline? Thumbnail


Authors

Dr TIM CARD tim.card@nottingham.ac.uk
Clinical Associate Professor

Christian D Mallen

Michael Doherty



Abstract

Objectives: To examine incidence of treatment changes due to abnormal blood-test results and, to explore rates of treatment changes due to liver, kidney and haematological blood-test abnormalities in autoimmune rheumatic diseases (AIRD) treated with low-dose methotrexate or leflunomide.

Methods: Data for people with AIRDs prescribed methotrexate or leflunomide were extracted from the Clinical Practice Research Datalink. Participants were followed-up from first prescription of methotrexate or leflunomide in primary-care. Primary outcome of interest was drug discontinuation, defined as a prescription gap of ≥90 days following an abnormal (or severely abnormal) blood-test result. Dose reduction was examined between consecutive prescriptions. Incidence rates per 1,000 person-years were calculated.

Results: 15,670 and 2,689 participants contributing 46,571 and 4,558 person-years follow-up were included in methotrexate and leflunomide cohorts respectively. The incidence of methotrexate and leflunomide discontinuation with abnormal (severely abnormal) blood-test was 42.24(6.16) and 106.53(9.42)/1,000 person-years in year-1, and 22.44(2.84) and 31.69(4.40)/1,000 person-years respectively thereafter. The cumulative incidence of methotrexate and leflunomide discontinuation with abnormal (severely abnormal) blood-tests was 1 in 24(1 in 169), 1 in 9(1 in 106) at 1-year; and 1 in 45(1 in 352), 1 in 32(1 in 227) per-year respectively thereafter. Raised liver enzymes were the commonest abnormality associated with drug discontinuation. Methotrexate and leflunomide dose reduction incidence were comparable in year-1, however, thereafter methotrexate dose was reduced more often than leflunomide (16.60(95% CI; 13.05-21.13) vs. 8.10(95% CI; 4.97-13.20)/1,000 person-years).

Conclusion: Methotrexate and leflunomide were discontinued for blood-test abnormalities after year-1 of treatment, however, discontinuations for severely abnormal results were uncommon.

Citation

Nakafero, G., Grainge, M. J., Card, T., Mallen, C. D., Zhang, W., Doherty, M., …Abhishek, A. (2021). What is the incidence of methotrexate or leflunomide discontinuation related to cytopenia, liver enzyme elevation or kidney function decline?. Rheumatology, 60(12), 5785-5794. https://doi.org/10.1093/rheumatology/keab254

Journal Article Type Article
Acceptance Date Mar 5, 2021
Online Publication Date Mar 16, 2021
Publication Date Dec 1, 2021
Deposit Date Mar 17, 2021
Publicly Available Date Mar 17, 2022
Journal Rheumatology
Electronic ISSN 1462-0324
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 60
Issue 12
Pages 5785-5794
DOI https://doi.org/10.1093/rheumatology/keab254
Keywords Autoimmune rheumatic diseases, Methotrexate, Leflunomide, Blood-test monitoring
Public URL https://nottingham-repository.worktribe.com/output/5399000
Publisher URL https://academic.oup.com/rheumatology/article/60/12/5785/6174126

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