SynthesisRheumatology (Oxford, England)2021
Prevalence and predictors of adverse events with methotrexate mono- and combination-therapy for rheumatoid arthritis: a systematic review.
Synthesis in Rheumatology (Oxford, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Comparative efficacy and safety of JAK inhibitors as monotherapy and in combination with methotrexate in patients with active rheumatoid arthritis: A systematic review and meta-analysis.Frontiers in immunology · 2022Pooled it
- Low-dose IL-2 improved clinical symptoms by restoring reduced regulatory T cells in patients with refractory rheumatoid arthritis: A randomized controlled trial.Frontiers in immunology · 2022Trial
- Agranulocytosis associated with metamizole among EudraVigilance reports involving methotrexate for rheumatoid arthritis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A comprehensive review on thermo-responsive targeted and functional therapy for management of rheumatoid arthritis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- The obesity-inflammation axis in psoriatic disease: mechanisms and therapeutic strategies.Nature reviews. Rheumatology · 2026Review
- Methotrexate Maintenance After Initiation of Biological or Targeted Synthetic DMARDs in Rheumatoid Arthritis: Results from the 2-Year Longitudinal Prospective Non-interventional STRATEGE2 Study.Rheumatology and therapy · 2026Article
- Development of a Complex Biofeedback-Based Intervention to Improve Methotrexate Adherence in Rheumatoid Arthritis: A COM-B Model Informed Qualitative Study.Patient preference and adherence · 2026Article
- Observational
- Drug-induced interstitial lung disease: a pharmacovigilance study of twelve immunomodulatory and antineoplastic agents.Journal of pharmaceutical health care and sciences · 2025Article
- Acute Transient Aminotransferase Elevation is Common With Intrathecal Methotrexate, but Liver Injury is Infrequent.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Ivarmacitinib reduces the need for adding/escalating medications in moderate-to-severe rheumatoid arthritis patients: aFrontiers in pharmacology · 2025Article
- Analysis of factors influencing target PASI responses and side effects of methotrexate monotherapy in plaque psoriasis: a multicenter study of 1521 patients.Archives of dermatological research · 2024Article
- Risk Factors Associated with Adverse Events Leading to Methotrexate Withdrawal in Elderly Rheumatoid Arthritis Patients: A Retrospective Cohort Study.Journal of clinical medicine · 2024Article
- Relationship between frailty and methotrexate discontinuation due to adverse events in rheumatoid arthritis patients.Clinical rheumatology · 2023Article
- Selection of treatment regimens based on shared decision-making in patients with rheumatoid arthritis on remission in the FREE-J study.Rheumatology (Oxford, England) · 2022Article
- Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study.Rheumatology (Oxford, England) · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesThis systematic review aims to summarize rates of adverse events (AEs) in patients with RA or inflammatory arthritis starting MTX as monotherapy or in combination with other csDMARDs, and to identify reported predictors of AEs.
methodsThree databases were searched for studies reporting AEs in MTX-naïve patients with RA. Randomized controlled trials (RCTs) and observational cohort studies were included. Prevalence rates of AEs were pooled using random effects meta-analysis, stratified by study design.
resultsForty-six articles (34 RCTs and 12 observational studies) were identified. The pooled prevalence of total AEs was 80.1% in RCTs (95% CI: 73.5, 85.9), compared with 23.1% in observational studies (95% CI: 12.3, 36.0). The pooled prevalence of serious AEs was 9.5% in RCTs (95% CI: 7.4, 11.7), and 2.1% in observational studies (95% CI: 1.0, 3.4). MTX discontinuation due to AEs was higher in observational studies (15.5%, 95% CI: 9.6, 22.3) compared with RCTs (6.7%, 95% CI: 4.7, 8.9). Gastrointestinal events were the most commonly reported AEs (pooled prevalence: 32.7%, 95% CI: 18.5, 48.7). Five studies examined predictors of AEs. RF status, BMI and HAQ score were associated with MTX discontinuation due to AEs; ACPA negativity, smoking and elevated creatinine were associated with increased risk of elevated liver enzymes.
conclusionThe review provides an up-to-date overview of the prevalence of AEs associated with MTX in patients with RA. The findings should be communicated to patients to help them make informed choices prior to commencing MTX.
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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.