Trial reportArthritis research & therapy2015
Comparison of two different folic acid doses with methotrexate--a randomized controlled trial (FOLVARI Study).
Trial report in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 15 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.
Randomized Trial of 10 mg Versus 30 mg Per Week of Folic Acid in Combination With Methotrexate in Rheumatoid Arthritis
Evaluating the Efficacy of Weekly Folic Acid in Pediatric Inflammatory Bowel Disease Patients on Methotrexate
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Low-Dose Methotrexate and Mucocutaneous Adverse Events: Results of a Systematic Literature Review and Meta-Analysis of Randomized Controlled Trials.Arthritis care & research · 2020Pooled 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
- Comparison of the impact of Tripterygium wilfordii Hook F and Methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow up of a randomized, non-blinded, controlled study.Arthritis research & therapy · 2018Trial
- High-dose folic acid supplement is associated with increased cardiovascular risk in rheumatoid arthritis patients on methotrexate.Therapeutic advances in musculoskeletal disease · 2026Article
- Folate from probiotic bacteria and its therapeutic applications.Archives of microbiology · 2025Review
- Oral Diseases During Systemic Psoriatic Drugs: A Review of the Literature and Case Series.Dermatology practical & conceptual · 2024Review
- [Methotrexate treatment before use of biologics in rheumatoid arthritis : Analysis of guideline compliance].Zeitschrift fur Rheumatologie · 2023Article
- Long-term persistence of oral methotrexate and associated factors in rheumatoid arthritis: a retrospective cohort study.Rheumatology international · 2023Article
- Observational
- Article
- Teasing out Artificial Intelligence in Medicine: An Ethical Critique of Artificial Intelligence and Machine Learning in Medicine.Journal of bioethical inquiry · 2021Article
- A Review of Clinical Applications and Side Effects of Methotrexate in Ophthalmology.Journal of ophthalmology · 2020Review
- Clinico-genetic model to predict methotrexate intolerance in rheumatoid arthritis.Clinical rheumatology · 2020Article
- Acute versus chronic methotrexate poisoning; a cross-sectional study.BMC pharmacology & toxicology · 2019Article
- Precursor miR-499a Variant but not miR-196a2 is Associated with Rheumatoid Arthritis Susceptibility in an Egyptian Population.Molecular diagnosis & therapy · 2016Article
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 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThere is reasonable evidence that folic acid 5-10 mg per week leads to reduction in methotrexate (MTX) toxicity in rheumatoid arthritis (RA). However, this is based on studies conducted with lower MTX dosage than used currently. It is unclear whether higher doses of folic acid may be better in reducing toxicity.
methodsThis was a double-blind randomized controlled trial of 24 weeks duration. To be eligible, patients should have rheumatoid arthritis (1987 American College of Rheumatology criteria), be 18-75 years of age, not be on MTX and have active disease as defined by 'Modified Disease Activity Score using three variables' (DAS28(3)) > 3.2. MTX was started at 10 mg/week and escalated to 25 mg/week by 12 weeks. Folic acid was given at a dose of 10 mg (FA10) or 30 mg per week (FA30). Co-primary endpoints were incidence of toxicity (undesirable symptoms and laboratory abnormalities) and change in disease activity by 24 weeks. Intention-to-treat and per-protocol analyses were performed.
resultsAmong 100 patients enrolled, 51 and 49 were randomized to FA10 and FA30 respectively. By 24 weeks, there were 6 patient withdrawals in either group and mean(±SD) dose of MTX was 22.8 ± 4.4 and 21.4 ± 4.6 mg per week (p = 0.1). Frequency of patients with undesirable symptoms was non-significantly lower by 7.4% (95% confidence interval -27.4 to 12.7%) in FA10 compared to FA30. There was also no difference in frequency of transaminitis (>Upper limit of normal (ULN)) (42.6, 45.7%, p = 0.7) or transminitis as per primary endpoint (>2xULN) (10.6, 8.7%, p = 1.0) or cytopenias (4.3, 4.3%, p = 0.9). There was no difference in the primary end-point of occurrence of any adverse effect (symptom or laboratory) in FA10 and FA30 (46.8, 54.3%, p = 0.5). At 24 weeks, DAS28(3) declined in both groups by a similar extent (-1.1 ± 1.0, -1.3 ± 1.0, p = 0.2) and 'European League Against Rheumatism' good or moderate response occurred in 56.9 and 67.4% (p = 0.3).
conclusionsEven with the high doses of MTX used in current practice, there was no additional benefit (or harm) of a higher dose of folic acid (30 mg/week) over a usual dose (10 mg/week).
trial registrationClinicaltrials.gov NCT01583959 Registered 15 March 2012.
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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.