Supplementation with Folic Acid during Methotrexate Therapy for Rheumatoid Arthritis: A Double-Blind, Placebo-Controlled Trial

@article{Morgan1994SupplementationWF,
  title={Supplementation with Folic Acid during Methotrexate Therapy for Rheumatoid Arthritis: A Double-Blind, Placebo-Controlled Trial},
  author={Sarah L. Morgan and Joseph E. Baggott and W. H. Vaughn and J S Austin and T A Veitch and Ji Yeon Lee and William J. Koopman and Carlos L. Krumdieck and Graciela S Alarc{\'o}n},
  journal={Annals of Internal Medicine},
  year={1994},
  volume={121},
  pages={833-841}
}
The folic acid antagonist methotrexate (n-10-methyl-aminopterin) is useful in low doses (2.5 to 20 mg/wk) for treating chronic inflammatory diseases [1-7]. Many trials have established the efficacy of methotrexate in rheumatoid arthritis [7-13]. Compared with other disease-modifying drugs, methotrexate has the highest probability of drug continuation at 10 years. Dose response-related toxic effects have been reported in 30% to 90% of patients given methotrexate [13]. Toxic effects include… Expand

Paper Mentions

Interventional Clinical Trial
The aim of the this study is to evaluate the effectiveness of methotrexate added to treatment as usual on positive and negative symptoms, cognitive and social functioning and quality of… Expand
ConditionsSchizoaffective Disorder, Schizophrenia, Schizophreniform Disorder
InterventionDrug
Interventional Clinical Trial
This study looks at how the arthritis drug methotrexate works in low doses to treat rheumatoid arthritis. (High doses of methotrexate are used to treat some types of cancer… Expand
ConditionsAdjuvant Arthritis, Rheumatoid Arthritis
InterventionDietary Supplement, Drug
Do patients with rheumatoid arthritis established on methotrexate and folic acid 5 mg daily need to continue folic acid supplements long term?
TLDR
It is important to continue FA supplementation over the long term in patients on methotrexate and FA in order to prevent them discontinuing treatment because of mouth ulcers or nausea and vomiting. Expand
Methotrexate in Rheumatoid Arthritis
TLDR
It is recommended that folic acid should be empirically supplemented in all patients at the initiation of methotrexate therapy, associated with a high benefit: risk ratio and is likely to be cost effective. Expand
Efficacy of folinic acid in reducing methotrexate toxicity in juvenile idiopathic arthritis.
TLDR
Folinic acid supplementation resulted in a significant reduction in the most common side effects of MTX, without affecting the clinical efficacy of the drug. Expand
Folic Acid and Folinic Acid for Reducing Side Effects in Patients Receiving Methotrexate for Rheumatoid Arthritis
TLDR
A protective effect of supplementation with either folic or folinic acid for patients with RA during treatment with MTX is supported, with a clinically important significant reduction shown in the incidence of GI side effects and hepatic dysfunction. Expand
Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study.
TLDR
Both folate supplementation regimens reduced the incidence of elevated liver enzyme levels during MTX therapy, and as a consequence, MTX was discontinued less frequently in these patients. Expand
Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis.
TLDR
It does not appear that supplementation with either folic or folinic acid has a statistically significant effect on the efficacy of MTX in treating RA, and the quality of the evidence was rated as 'moderate' for each outcome as assessed by GRADE. Expand
Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis. An update and proposals for guidelines.
TLDR
An individually adjusted supply of folic acid rather than folinic acid is proposed for supplementation during methotrexate therapy of patients with rheumatoid arthritis, addressing both the timing of folate supplementation and the weekly folate-to-methotrexate ratio. Expand
Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review.
TLDR
The use of supplemental folates, including folic and folinic acid, in RA patients treated with MTX has been shown to improve continuation rates by reducing the incidence of liver function test abnormalities and gastrointestinal intolerance and it is proposed that folic acid supplements be prescribed routinely to all patients receiving MTX for the treatment of RA. Expand
Comparison of two different folic acid doses with methotrexate – a randomized controlled trial (FOLVARI Study)
TLDR
Even with the high doses of MTX used in current practice, there was no additional benefit (or harm) of a higher dose of folic acid over a usual dose (10 mg/week) and the primary end-point of occurrence of any adverse effect in FA10 and FA30 was no difference. Expand
A Pilot Randomized Controlled Double-Blind Trial of High- Versus Low-Dose Weekly Folic Acid in People With Rheumatoid Arthritis Receiving Methotrexate.
TLDR
Reducing the dose of supplemental folic acid used in conjunction with methotrexate (MTX) therapy in people with active rheumatoid arthritis improved disease control and/or increased MTX-related adverse effects, and a reduction in RBC folate secondary to reduction in folic Acid dose was not associated with a change in RA disease activity orMTX- related adverse effects. Expand
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References

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TLDR
It is concluded that a daily supplement of 1 mg of FA during low-dose MTX therapy (median dose 7.5 mg/week [16.4 mumoles]) is usefull in lessening toxicity without altering efficacy during the first 6 months of treatment. Expand
Administration of folinic acid after low dose methotrexate in patients with rheumatoid arthritis.
TLDR
While the incidence of stomatitis and gastrointestinal toxicity were lower during leucovorin treatment, the study lacked sufficient power to establish a statistically significant difference. Expand
Folate supplementation in methotrexate-treated rheumatoid arthritis patients.
TLDR
It is suggested that elevation of MCV in RA patients treated simultaneously with MTX and folate does not predict MTX toxicity, and the mechanism of action of MTX with regard to folate metabolism is discussed. Expand
Folate status of rheumatoid arthritis patients receiving long-term, low-dose methotrexate therapy.
TLDR
Analysis of variance demonstrated that the specific activity of the enzyme system in lymphocytes was significantly lower in the MTX-treated group, with an activity approximately one-half that of the control and the non-MTX- treated groups. Expand
Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis. Results of a multicenter randomized, double-blind, placebo-controlled trial.
TLDR
The methotrexate-leucovorin protocol used significantly reduces common side effects of methotreysate therapy without significantly altering efficacy. Expand
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TLDR
While there was considerable improvement in nausea during the study, the effect of folinic acid could not be differentiated from that of placebo and it seems likely that polyglutamated tissue stores of MTX do not contribute to drug efficacy and in this format folinic Acid could not been shown to be more useful than placebo in reducing drug induced nausea. Expand
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TLDR
High-dose leucovorin (folinic acid) supplementation was tested in a prospective, unblinded manner for 4 weeks in 7 rheumatoid arthritis patients who were being treated successfully with low-dose methotrexate (MTX); however, the underlying rheumatic disease worsened in all patients. Expand
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TLDR
It is concluded that excerbation of rheumatoid arthritis is likely when folinic acid is given shortly after the weekly dose of methotrexate. Expand
Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis.
TLDR
A general trend, although not significant, was found toward a dose toxicity relationship, and a general trend occurred more commonly with MTX. Expand
Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial.
TLDR
Patients able to tolerate low-dose pulse MTX therapy were significantly improved, compared with patients receiving placebo therapy, for all clinical variables measured, including joint pain/tenderness and swelling counts, rheumatoid nodules, and patient and physician assessment of disease activity. Expand
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