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Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity.
Semin Arthritis Rheum 1998; 27(5):277-92SA

Abstract

OBJECTIVES

To provide an update of the current knowledge of the mechanism of action of low-dose methotrexate (MTX) in the treatment of patients with rheumatoid arthritis (RA), with an emphasis on the mechanisms involved in toxicity. We also considered strategies currently used to prevent or decrease toxicity of MTX.

METHODS

We reviewed the literature dealing with the subjects of MTX treatment of RA, the mechanisms of action of low-dose MTX regarding efficacy and toxicity, and strategies used to prevent or decrease MTX toxicity.

RESULTS

MTX is a fast working and effective second-line antirheumatic agent (SLA). Its use is limited mainly because of side effects. The mechanisms of action regarding efficacy and toxicity are probably determined by different metabolic pathways. Recent data indicate that the antiinflammatory effect of MTX is mediated by adenosine. However, MTX side effects can only partly be explained by folate antagonism and may also depend on its action on other related metabolic pathways. The latter include the homocysteine-methionine-polyamine pathway and purine metabolism. Variants in these metabolic routes (ie, the C677T mutation in the methylene-tetrahydrofolate reductase [MTHFR] gene), may predispose to the development of side effects. Currently the most promising strategy to decrease or prevent toxicity of MTX is concomitant prescription of folic acid or folinic acid. Other strategies are currently under investigation.

CONCLUSIONS

MTX benefits a majority of RA patients. Approximately 30% of patients, however, abandon treatment because of drug-related side effects. Folic acid or folinic acid likely reduces MTX toxicity. More data, however, are needed to evaluate a potential detrimental effect on the antirheumatic efficacy of MTX.

Authors+Show Affiliations

Department of Rheumatology, University of Nijmegen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

9572710

Citation

van Ede, A E., et al. "Methotrexate in Rheumatoid Arthritis: an Update With Focus On Mechanisms Involved in Toxicity." Seminars in Arthritis and Rheumatism, vol. 27, no. 5, 1998, pp. 277-92.
van Ede AE, Laan RF, Blom HJ, et al. Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Semin Arthritis Rheum. 1998;27(5):277-92.
van Ede, A. E., Laan, R. F., Blom, H. J., De Abreu, R. A., & van de Putte, L. B. (1998). Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Seminars in Arthritis and Rheumatism, 27(5), pp. 277-92.
van Ede AE, et al. Methotrexate in Rheumatoid Arthritis: an Update With Focus On Mechanisms Involved in Toxicity. Semin Arthritis Rheum. 1998;27(5):277-92. PubMed PMID: 9572710.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. AU - van Ede,A E, AU - Laan,R F, AU - Blom,H J, AU - De Abreu,R A, AU - van de Putte,L B, PY - 1998/5/8/pubmed PY - 1998/5/8/medline PY - 1998/5/8/entrez SP - 277 EP - 92 JF - Seminars in arthritis and rheumatism JO - Semin. Arthritis Rheum. VL - 27 IS - 5 N2 - OBJECTIVES: To provide an update of the current knowledge of the mechanism of action of low-dose methotrexate (MTX) in the treatment of patients with rheumatoid arthritis (RA), with an emphasis on the mechanisms involved in toxicity. We also considered strategies currently used to prevent or decrease toxicity of MTX. METHODS: We reviewed the literature dealing with the subjects of MTX treatment of RA, the mechanisms of action of low-dose MTX regarding efficacy and toxicity, and strategies used to prevent or decrease MTX toxicity. RESULTS: MTX is a fast working and effective second-line antirheumatic agent (SLA). Its use is limited mainly because of side effects. The mechanisms of action regarding efficacy and toxicity are probably determined by different metabolic pathways. Recent data indicate that the antiinflammatory effect of MTX is mediated by adenosine. However, MTX side effects can only partly be explained by folate antagonism and may also depend on its action on other related metabolic pathways. The latter include the homocysteine-methionine-polyamine pathway and purine metabolism. Variants in these metabolic routes (ie, the C677T mutation in the methylene-tetrahydrofolate reductase [MTHFR] gene), may predispose to the development of side effects. Currently the most promising strategy to decrease or prevent toxicity of MTX is concomitant prescription of folic acid or folinic acid. Other strategies are currently under investigation. CONCLUSIONS: MTX benefits a majority of RA patients. Approximately 30% of patients, however, abandon treatment because of drug-related side effects. Folic acid or folinic acid likely reduces MTX toxicity. More data, however, are needed to evaluate a potential detrimental effect on the antirheumatic efficacy of MTX. SN - 0049-0172 UR - https://www.unboundmedicine.com/medline/citation/9572710/Methotrexate_in_rheumatoid_arthritis:_an_update_with_focus_on_mechanisms_involved_in_toxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0049-0172(98)80049-8 DB - PRIME DP - Unbound Medicine ER -