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

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., Taal, M. W., Aithal, G. P., & 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