ArticleRheumatology (Oxford, England)2021
What is the incidence of methotrexate or leflunomide discontinuation related to cytopenia, liver enzyme elevation or kidney function decline?
Article in Rheumatology (Oxford, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Blood-test monitoring strategies for patients established on immune-suppressing drugs: a mixed-methods study.Health technology assessment (Winchester, England) · 2026Pooled it
- Praziquantel ameliorates leflunomide-induced nephrotoxicity in mice: a novel therapeutic approach targeting TGF-β/Smad/Wnt/β-catenin/NF-κB/PPAR-γ signaling and Nrf-2.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- In vitro anti-inflammatory potential and in vivo anti-arthritis activities of Ximenia caffra extract on antigen-induced arthritis in rats.Scientific reports · 2026Article
- Assessing the Impact of Metabolic Syndrome on Liver Outcomes in Methotrexate Users: A Retrospective Cohort Study.Journal of clinical medicine · 2025Article
- Patient and health professional views on risk-stratified monitoring of immune-suppressing treatment in adults with inflammatory diseases.Rheumatology (Oxford, England) · 2025Article
- Acute Transient Aminotransferase Elevation is Common With Intrathecal Methotrexate, but Liver Injury is Infrequent.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Risk-stratified monitoring for sulfasalazine toxicity: prognostic model development and validation.RMD open · 2024Article
- Forty-Eight-Month Monitoring of Disease Activity in Patients with Long-Standing Rheumatoid Arthritis Treated with TNF-α Inhibitors: Time for Clinical Outcome Prediction and Biosimilar vs Biologic Originator Performance.Clinical drug investigation · 2024Observational
- Risk-stratified monitoring for thiopurine toxicity in immune-mediated inflammatory diseases: prognostic model development, validation, and, health economic evaluation.EClinicalMedicine · 2023Article
- Risk stratified monitoring for methotrexate toxicity in immune mediated inflammatory diseases: prognostic model development and validation using primary care data from the UK.BMJ (Clinical research ed.) · 2023Article
- Attitudes and practices in the laboratory monitoring of conventional synthetic disease modifying anti-rheumatic drugs by rheumatologists and rheumatology trainees.BMC rheumatology · 2022Article
- Article
- Development and validation of a prognostic model for leflunomide discontinuation with abnormal blood tests during long-term treatment: cohort study using data from the Clinical Practice Research Datalink Gold and Aurum.Rheumatology (Oxford, England) · 2022Article
- Article
- Incidence and pattern of mycophenolate discontinuation associated with abnormal monitoring blood-test results: cohort study using data from the Clinical Practice Research Datalink Aurum.Rheumatology advances in practice · 2022Article
- High Efficacy Combined Microneedles Array with Methotrexate Nanocrystals for Effective Anti-Rheumatoid Arthritis.International journal of nanomedicine · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivesTo 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 MTX or LEF.
methodsData for people with AIRDs prescribed MTX or LEF were extracted from the Clinical Practice Research Datalink. Participants were followed-up from first prescription of MTX or LEF 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 1000 person-years were calculated.
results15, 670 and 2,689 participants contributing 46, 571 and 4,558 person-years follow-up were included in MTX and LEF cohorts, respectively. The incidence of MTX and LEF discontinuation with abnormal (severely abnormal) blood-test was 42.24 (6.16) and 106.53 (9.42)/1000 person-years in year 1, and 22.44 (2.84) and 31.69 (4.40)/1000 person years, respectively, thereafter. The cumulative incidence of MTX and LEF 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. MTX and LEF dose reduction incidence were comparable in year 1, however, thereafter MTX dose was reduced more often than LEF [16.60 (95% CI 13.05, 21.13) vs 8.10 (95% CI 4.97, 13.20)/1000 person-years].
conclusionMTX and LEF were discontinued for blood-test abnormalities after year 1 of treatment, however, discontinuations for severely abnormal results were uncommon.
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