SynthesisAnnals of the rheumatic diseases2009
Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis.
Synthesis in Annals of the rheumatic diseases, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 7 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
51 citing papers in PubMed, 7 syntheses or guidelines pooled it, 178 citations in OpenAlex.
- Can Methotrexate Monotherapy Achieve Clinical Remission in Patients with Active Rheumatoid Arthritis? A Model-Based Meta-Analysis.Journal of clinical pharmacology · 2025Pooled it
- Comparison of the Efficacy and Safety of Disease-Modifying Antirheumatic Drugs Combination Therapies: A Systematic Review and Network Meta-Analysis.Clinical and translational science · 2025Pooled it
- 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.Arthritis care & research · 2021Guideline
- Efficacy and safety of total glucosides of paeony combined with methotrexate and leflunomide for active rheumatoid arthritis: a meta-analysis.Drug design, development and therapy · 2019Pooled it
- Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study.BMJ (Clinical research ed.) · 2015Pooled it
- EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update.Annals of the rheumatic diseases · 2014Guideline
- Methotrexate monotherapy versus methotrexate combination therapy with non-biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis.The Cochrane database of systematic reviews · 2010Pooled it
- Defining and characterizing sustained remission in patients with rheumatoid arthritis.Clinical rheumatology · 2018Trial
- Effects of Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Response to Periodontal Treatment in Patients with Rheumatoid Arthritis.BioMed research international · 2018Trial
- Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre-Specified Analysis of Two Phase III Trials.Arthritis care & research · 2016Trial
- Randomised comparison of initial triple DMARD therapy with methotrexate monotherapy in combination with low-dose glucocorticoid bridging therapy; 1-year data of the tREACH trial.Annals of the rheumatic diseases · 2014Trial
- A randomized placebo-controlled trial of methotrexate in psoriatic arthritis.Rheumatology (Oxford, England) · 2012Trial
- Narrative review on the development of multi-target pharmacological agents for the management of rheumatoid arthritis.Inflammopharmacology · 2026Review
- Liver Enzyme Elevations in Rheumatoid Arthritis: Clinical Relevance and Influence on Treatment Strategies.Journal of clinical medicine · 2025Article
- Dual Targeting Biomimetic Carrier-Free Nanosystems for Photo-Chemotherapy of Rheumatoid Arthritis via Macrophage Apoptosis and Re-Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integration of genomics, clinical characteristics and baseline biological profiles to predict the risk of liver injury induced by high-dose methotrexate.Frontiers in pharmacology · 2024Article
- Use of transient elastography to assess hepatic steatosis and fibrosis in patients with juvenile idiopathic arthritis during methotrexate treatment.Clinical rheumatology · 2024Article
- Combination Therapy for Psoriasis with Methotrexate and Other Oral Disease-Modifying Antirheumatic Drugs: A Systematic Review.Dermatology and therapy · 2023Review
- Experiences and Treatment Preferences in Patients With Psoriatic Arthritis: A Cross-Sectional Study in the ArthritisPower Registry.Rheumatology and therapy · 2022Article
- Quinoline-based fluorescent probe for the detection and monitoring of hypochlorous acid in a rheumatoid arthritis model.RSC advances · 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
4 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo evaluate the efficacy and toxicity of methotrexate (MTX) monotherapy compared with MTX combination with non-biological disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis.
methodA systematic review of randomised trials comparing MTX alone and in combination with other non-biological DMARDs was carried out. Trials were identified in Medline, EMBASE, the Cochrane Library and ACR/EULAR meeting abstracts. Primary outcomes were withdrawals for adverse events or lack of efficacy.
resultsA total of 19 trials (2025 patients) from 6938 citations were grouped by the type of patients randomised. Trials in DMARD naive patients showed no significant advantage of the MTX combination versus monotherapy; withdrawals for lack of efficacy or toxicity were similar in both groups (relative risk (RR) = 1.16; 95% CI 0.70 to 1.93). Trials in MTX or non-MTX DMARD inadequate responder patients also showed no difference in withdrawal rates between the MTX combo versus mono groups (RR = 0.86; 95% CI 0.49 to 1.51 and RR = 0.75; 95% CI 0.41 to 1.35), but in one study the specific combination of MTX with sulfasalazine and hydroxychloroquine showed a better efficacy/toxicity ratio than MTX alone with RR = 0.3 (95% CI 0.14 to 0.65). Adding leflunomide to MTX non-responders improved efficacy but increased the risk of gastrointestinal side effects and liver toxicity. Withdrawals for toxicity were most significant with ciclosporin and azathioprine combinations.
conclusionIn DMARD naive patients the balance of efficacy/toxicity favours MTX monotherapy. In DMARD inadequate responders the evidence is inconclusive. Trials are needed that compare currently used MTX doses and combination therapies.
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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.