ArticleACR open rheumatology2020
Adverse Effects of Low-Dose Methotrexate in a Randomized Double-Blind Placebo-Controlled Trial: Adjudicated Hematologic and Skin Cancer Outcomes in the Cardiovascular Inflammation Reduction Trial.
Article in ACR open rheumatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- II Consensus of the Brazilian Society of Dermatology for the treatment of alopecia areata.Anais brasileiros de dermatologiaGuideline
- Systemic Immune-Inflammation Index as a Marker of Activity in Behcet's Uveitis.Clinical medicine insights. Arthritis and musculoskeletal disorders · 2026Article
- Low Dose Methotrexate Has Divergent Effects on Cycling and Resting Human Hematopoietic Stem and Progenitor Cells.Clinical and translational science · 2025Article
- Patient-Centric Approach for the Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease in Older People.Drugs & aging · 2025Review
- Methotrexate - Safe Backbone for the Treatment of Rheumatoid Arthritis.Current rheumatology reviews · 2025Review
- Ultra-High-Performance Liquid Chromatography-High-Definition Mass Spectrometry-Based Metabolomics to Reveal the Potential Anti-Arthritic Effects ofMetabolites · 2024Article
- Skin Malignancies Due to Anti-Cancer Therapies.Cancers · 2024Review
- One-carbon unit supplementation fuels purine synthesis in tumor-infiltrating T cells and augments checkpoint blockade.Cell chemical biology · 2024Article
- Article
- One-carbon unit supplementation fuels tumor-infiltrating T cells and augments checkpoint blockade.bioRxiv : the preprint server for biology · 2023Article
- Low-Dose Methotrexate and Serious Adverse Events Among Older Adults With Chronic Kidney Disease.JAMA network open · 2023Article
- Skin Cancer Correlations in Psoriatic Patients.Cancers · 2023Review
- The Optimal Management of Inflammatory Bowel Disease in Patients with Cancer.Journal of clinical medicine · 2023Review
- Use of methotrexate and risk of skin cancer: a nationwide case-control study.British journal of cancer · 2023Article
- Risk of malignant melanoma and non-melanoma skin cancer in rheumatoid arthritis patients initiating methotrexate versus hydroxychloroquine: a cohort study.Clinical and experimental rheumatology · 2023Article
- [Management of inflammatory rheumatic diseases during and after malignancies].Zeitschrift fur Rheumatologie · 2022Article
- Implications of Evolving Disease Classification for Drug Approval in Juvenile Idiopathic Arthritis.Paediatric drugs · 2022Article
- Immunotargets and Therapy for Prurigo Nodularis.ImmunoTargets and therapy · 2022Review
- High MW polyethylene glycol prolongs circulation of pegloticase in mice with anti-PEG antibodies.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveLow-dose methotrexate (LD-MTX), a cornerstone in the treatment of rheumatoid arthritis, is associated with a moderately increased risk of anemia, leukopenia, and skin cancers, but the risks of myelosuppression and malignancy during LD-MTX use remain incompletely described. We examined the risks of cytopenias and skin cancers among patients taking LD-MTX versus placebo in a large randomized controlled trial (RCT).
methodsWe prespecified secondary analyses of a double-blind, placebo-controlled RCT that included adults with known cardiovascular disease and diabetes or metabolic syndrome in the United States and Canada. Subjects were randomly allocated to LD-MTX (20 mg/week maximum) or placebo. All subjects received folic acid (1 mg daily for 6days/week). We assessed the frequency of blindly adjudicated hematologic and malignant adverse events (AEs).
resultsA total of 2391 subjects were randomized to LD-MTX (mean dosage 14.9 mg/week), and 2395 were randomized to placebo. During follow-up, in the LD-MTX arm, simultaneous two-line cytopenias (n = 92 [3.9%]) or pancytopenia (n = 13 [0.54%]) were infrequent. Pancytopenia developed as soon as 4 months and as late as 3.5 years after beginning LD-MTX, though the latter subject had been recently diagnosed with multiple myeloma. Overall skin cancer risk was increased in users of LD-MTX compared with users of placebo, which driven largely by a statistically significant increased risk of squamous cell skin cancer (hazard ratio [HR] 3.31; 95% confidence interval [CI] 1.63-6.71). Melanoma was increased in LD-MTX, but this was not statistically significant (HR 2.33; 95% CI 0.60-9.01).
conclusionsAmong subjects using LD-MTX, simultaneous two-line cytopenias and pancytopenia were uncommon. We found more cases of skin cancer, particularly squamous cell carcinomas, in the LD-MTX arm than the placebo arm.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.