ArticlePloS one2016
Factors Associated with Myelosuppression Related to Low-Dose Methotrexate Therapy for Inflammatory Rheumatic Diseases.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Cytopenias among patients with rheumatic diseases using methotrexate: a meta-analysis of randomized controlled clinical trials.Rheumatology (Oxford, England) · 2020Pooled it
- Comparison of two doses of leucovorin in severe low-dose methotrexate toxicity - a randomized controlled trial.Arthritis research & therapy · 2023Trial
- Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: Rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study.Seminars in arthritis and rheumatism · 2017Trial
- Agranulocytosis associated with metamizole among EudraVigilance reports involving methotrexate for rheumatoid arthritis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Prescribing Inflammatory Bowel Disease Medications in Chronic Kidney Disease: A Practical Guide.Alimentary pharmacology & therapeutics · 2025Review
- Metabolic dysfunction-associated steatotic liver disease and cardiovascular risk factors in rheumatoid arthritis.Clinical rheumatology · 2025Article
- Epstein-Barr virus-positive mucocutaneous ulcer resulting in severe methotrexate intoxication: a case report.Journal of medical case reports · 2024Article
- Single Low-Dose Methotrexate and Vitamin B12 Deficiency-Induced Pancytopenia Causing Fatality: A Case Report.Cureus · 2024Article
- Plurality Over Parsimony: When Two Diagnoses Are More Likely Than One.Journal of general internal medicine · 2024Article
- Red Cell Distribution Width and Absolute Lymphocyte Count Associate With Biomarkers of Inflammation and Subsequent Mortality in Rheumatoid Arthritis.The Journal of rheumatology · 2023Article
- Agranulocytosis in systemic lupus erythematosus: A case report.Clinical case reports · 2022Article
- Nomogram predicting leukopenia in osteosarcoma after high-dose methotrexate chemotherapy.Aging · 2022Article
- Is there still a place for methotrexate in severe psoriatic arthritis?Therapeutic advances in musculoskeletal disease · 2022Review
- Methotrexate-Induced Septicemia With Severe Pancytopenia and Diffuse Cutaneous Ulcerative Lesions.Cureus · 2021Article
- Sustained Long-Term Retention Rates of Abatacept in Combination with Conventional Synthetic Disease-Modifying Antirheumatic Drugs in Elderly Patients with Rheumatoid Arthritis.Medicina (Kaunas, Lithuania) · 2021Observational
- Methotrexate-related toxicity in patients with rheumatoid arthritis and renal dysfunction.Rheumatology international · 2020Article
- Factors Predicting Severe Myelosuppression and Its Influence on Fertility in Patients with Low-Risk Gestational Trophoblastic Neoplasia Receiving Single-Agent Methotrexate Chemotherapy.Cancer management and research · 2020Article
- A Review of Clinical Applications and Side Effects of Methotrexate in Ophthalmology.Journal of ophthalmology · 2020Review
- Retention of tocilizumab with and without methotrexate during maintenance therapy for rheumatoid arthritis: the ACTRA-RI cohort study.Rheumatology (Oxford, England) · 2019Article
- Methotrexate and doxycycline interaction: a rare cause of pancytopenia.BMJ case reports · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveSevere myelosuppression is a serious concern in the management of rheumatic disease patients receiving methotrexate (MTX) therapy. This study was intended to explore factors associated with the development of MTX-related myelosuppression and its disease severity.
methodsWe retrospectively examined a total of 40 cases of MTX-related myelosuppression that had been filed in the registries of participating rheumatology and hematology divisions. Data before onset were compared with those of 120 controls matched for age and sex. Cytopenia was graded according to the National Cancer Institute criteria for adverse events. Data before and at onset were compared between the severe and non-severe groups.
resultsNon-use of folic acid supplements, concurrent medications, and low renal function were significantly associated with the development of myelosuppression (p < 0.001, p < 0.001, and p = 0.002, respectively). In addition, significantly lower MTX dosages, higher blood cell counts, and lower hemoglobin levels were seen in the myelosuppression group (p < 0.001). No patients exhibited leukocytopenia, neutropenia, or thrombocytopenia in routine blood monitoring taken within the past month. One-fourth developed myelosuppression within the first two months (an early-onset period). Myelosuppression was severe in approximately 40% of patients. Hypoalbuminemia and non-use of folic acid supplements were significantly associated with the severity of pancytopenia (p = 0.001 and 0.008, respectively). Besides these two factors, early onset and the use of lower doses of MTX were significantly associated with the severity of neutropenia (p = 0.003, 0.007, 0.003, and 0.002, respectively).
conclusionsMyelosuppression can occur abruptly at any time during low-dose MTX therapy, but severe neutropenia is more likely to occur in the early-onset period of this therapy. Contrary to our expectations, disease severity was not dependent on MTX doses. Serum albumin levels and folic acid supplementation are the important factors affecting the severity of MTX-related pancytopenia and neutropenia.
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