Trial reportAnnals of the rheumatic diseases2004
Differential effects of leflunomide and methotrexate on cytokine production in rheumatoid arthritis.
Trial report in Annals of the rheumatic diseases, 2004. 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, 64 citations in OpenAlex.
- Leflunomide for treating rheumatoid arthritis.The Cochrane database of systematic reviews · 2003Pooled it
- Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial.BMJ open · 2023Trial
- Safety and efficacy of leflunomide in primary Sjögren's syndrome: a phase II pilot study.Annals of the rheumatic diseases · 2007Trial
- Article
- Methotrexate Inhibits T Cell Proliferation but Not Inflammatory Cytokine Expression to Modulate Immunity in People Living With HIV.Frontiers in immunology · 2022Article
- Relationship Between Interleukin-6 -174G/C Genetic Variant and Efficacy of Methotrexate Treatment in Psoriatic Arthritis Patients.Pharmacogenomics and personalized medicine · 2021Article
- Achieving sustained minimal disease activity with methotrexate in early interleukin 23-driven early psoriatic arthritis.RMD open · 2020Article
- Traditional Chinese medicine Biqi capsule compared with leflunomide in combination with methotrexate in patients with rheumatoid arthritis: a randomized controlled trial.Chinese medicine · 2020Article
- Leflunomide: an unlikely trigger and mechanistically a beneficial drug for alopecia areata.Clinical rheumatology · 2019Article
- Synovial tissue research: a state-of-the-art review.Nature reviews. Rheumatology · 2017Review
- Rheumatoid Arthritis Pharmacotherapies: Do They Have Anti-Atherosclerotic Activity?Current rheumatology reports · 2016Review
- 1-Methyl-tryptophan synergizes with methotrexate to alleviate arthritis in a mouse model of arthritis.Autoimmunity · 2014Article
- Methotrexate and a spleen tyrosine kinase inhibitor cooperate to inhibit responses to peripheral blood B cells in rheumatoid arthritis.Pharmacology research & perspectives · 2013Article
- Reduction of plasma IL-6 but not TNF-α by methotrexate in patients with early rheumatoid arthritis: a potential biomarker for radiographic progression.Clinical rheumatology · 2013Article
- How does Chinese medicine target cytokine imbalance in rheumatoid arthritis?Chinese journal of integrative medicine · 2013Review
- Combination of MTX and LEF attenuates inflammatory bone erosion by down-regulation of receptor activator of NF-kB ligand and interleukin-17 in type II collagen-induced arthritis rats.Rheumatology international · 2013Article
- Gene Expression Profile of T-cell Receptors in the Synovium, Peripheral Blood, and Thymus during the Initial Phase of Collagen-induced Arthritis.Immune network · 2011Article
- Perioperative management of immunosuppression in rheumatic diseases--what to do?Rheumatology international · 2010Review
- Patient demographics and disease variables correlate with distinct cytokine patterns in mitogen-stimulated peripheral blood mononuclear cells from rheumatoid arthritis patients.Rheumatology international · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundT cells have a pivotal role in RA. Leflunomide inhibits pyrimidine biosynthesis, to which T cells are especially susceptible, and therefore may have a different cytokine profile than methotrexate. MATERIALS AND
methodsSerum samples of 100 patients with RA, treated with leflunomide (n = 50) or methotrexate (n = 50), were collected at baseline, after 16 weeks and after 1 year's treatment. Serum levels of interleukin 6 (IL6), and interferon (IFN) gamma were determined by ELISA. Additionally, peripheral blood mononuclear cells (PBMC) of five healthy volunteers and three patients with RA were isolated and the effects of the active metabolite of leflunomide (A77-1726, 0-200 mmol/l) on cell proliferation and on IL6 and IFNgamma production were determined by ELISA. In peripheral blood lymphocytes (PBL) and monocytes (PBM) from two healthy volunteers the effects of A77-1726 on IL6 production were measured by ELISA and PCR.
resultsMean (SEM) serum levels of IFNgamma were significantly reduced after leflunomide treatment (baseline 43 (10) pg/ml; 1 year 29 (7) (p = 0.015), but there was no change in IL6 levels (baseline 158 (41), 1 year 151 (48)). Both IFNgamma and IL6 levels were significantly reduced after methotrexate treatment. This observation was supported by in vitro experiments. The production of IFNgamma by PBL was inhibited by A77-1726, but IL6 production by PBM was not inhibited.
conclusionThe differential effect on IFNgamma and IL6 production supports the hypothesis that activated T cells are preferentially inhibited by leflunomide. An explanation may be either inhibition of uridine synthesis or effects on signal transduction pathways.
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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.