ReviewJoint bone spine2019
Methotrexate mechanism in treatment of rheumatoid arthritis.
Review in Joint bone spine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers, 6 of them syntheses 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
198 citing papers in PubMed, 6 syntheses or guidelines pooled it, 400 citations in OpenAlex.
- Association of folylpolyglutamate synthase polymorphisms with methotrexate response and toxicity in rheumatoid arthritis: a meta-analysis.The pharmacogenomics journal · 2026Pooled it
- Exosomes as Cellular Communicators and Therapeutic Agents in Orthopedic Diseases: From Mechanisms to Intervention.International journal of nanomedicine · 2026Pooled it
- Review of OxLDL Driven Inflammatory Cell Activation.Current atherosclerosis reports · 2025Pooled it
- Methotrexate for juvenile idiopathic arthritis.The Cochrane database of systematic reviews · 2024Pooled it
- Prevalence of Sarcopenia and its Association with Antirheumatic Drugs in Middle-Aged and Older Adults with Rheumatoid Arthritis: A Systematic Review and Meta-analysis.Calcified tissue international · 2021Pooled it
- Efficacy of methotrexate in reducing the risk of bone erosion in patients with rheumatoid arthritis: a systematic review of randomized controlled trials.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Pooled it
- Effect of different folic acid doses on methotrexate-related toxicity and its association with erythrocyte methotrexate-polyglutamates in patients with rheumatic diseases: a single-center exploratory randomized controlled trial.Clinical rheumatology · 2026Trial
- Genetics are not likely to offer clinically useful predictions for elevated liver enzyme levels in patients using low dose methotrexate.Seminars in arthritis and rheumatism · 2022Trial
- Combination of Methotrexate and Leflunomide Is Efficient and Safe for 60 Patients with Rheumatoid Arthritis.Computational and mathematical methods in medicine · 2022Trial
- Hypoxia as an amplifier of synovial inflammation in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Optimal timing of liver stiffness assessment in methotrexate-treated rheumatoid arthritis patients.Zeitschrift fur Rheumatologie · 2026Article
- Beyond the Prevention of Anti-drug Antibody Formation with Uricase Therapy: Mechanistic Roles of DMARDs in Modifying Gout Flare Risk.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Pharmacological assessment of drugs retained in the 1Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Modulation of TNF-α, IL-1β and myeloperoxidase contributes to the anti-inflammatory and analgesic effects of Paullinia pinnata Linn (Sapindaceae) extracts in complete Freund's adjuvant-induced mono-arthritis in rats.Journal of ethnopharmacology · 2026Article
- Review
- Osteoarthritis and rheumatoid arthritis: A comparative review of pathophysiology, diagnosis and evolving management.Journal of Taibah University Medical Sciences · 2026Review
- Regulatory Roles of Long Non-Coding RNAs in Methotrexate Pharmacology: Mechanistic and Translational Insights.Pharmaceutical research · 2026Review
- Methotrexate and glucocorticoid use in relation to cross-sectional and longitudinal associations of red blood cell distribution width in patients with rheumatoid arthritis.Nagoya journal of medical science · 2026Article
- Advances in methotrexate nano-formulations to enhance therapeutic efficacy against drug-resistant breast cancer.Discover nano · 2026Review
- [Methotrexate osteopathy-a critical review].Zeitschrift fur Rheumatologie · 2026Review
138 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Methotrexate has been used in treatment of rheumatoid arthritis (RA) since the 1980s and to this day is often the first line medication for RA treatment. In this review, we examine multiple hypotheses to explain the mechanism of methotrexate efficacy in RA. These include folate antagonism, adenosine signaling, generation of reactive oxygen species (ROS), decrease in adhesion molecules, alteration of cytokine profiles, and polyamine inhibition amongst some others. Currently, adenosine signaling is probably the most widely accepted explanation for the methotrexate mechanism in RA given that methotrexate increases adenosine levels and on engagement of adenosine with its extracellular receptors an intracellular cascade is activated promoting an overall anti-inflammatory state. In addition to these hypotheses, we examine the mechanism of methotrexate in RA from the perspective of its adverse effects and consider some of the newer genetic markers of methotrexate efficacy and toxicity in RA. Lastly, we briefly discuss the mechanism of additive methotrexate in the setting of TNF-α inhibitor treatment of RA. Ultimately, finding a clear explanation for the pathway and mechanism leading to methotrexate efficacy in RA, there may be a way to formulate more potent therapies with fewer side effects.
Indexed as
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.