Nakafero, G, Grainge, MJ, Card, T, Mallen, CD, Zhang, W, Doherty, M, Taal, MW, Aithal, GP and Abhishek, A (2021) What is the incidence of methotrexate or leflunomide discontinuation related to cytopenia, liver enzyme elevation or kidney function decline? Rheumatology. ISSN 1462-0332

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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.

Item Type: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: Autoimmune rheumatic diseases, Blood-test monitoring, Leflunomide, Methotrexate
Subjects: R Medicine > RC Internal medicine > RC927 Rheumatism
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Medicine and Health Sciences > School of Primary, Community and Social Care
Related URLs:
Depositing User: Symplectic
Date Deposited: 23 Mar 2021 15:27
Last Modified: 23 Mar 2021 15:31

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