An Update on Methotrexate

Juergen Brauna; Rolf Rau

Disclosures

Curr Opin Rheumatol. 2009;21(3):216-223. 

In This Article

Abstract and Introduction

Abstract

Purpose of review: Methotrexate (MTX) has been used for the treatment of rheumatoid arthritis (RA) for about three decades now. MTX is one of the most effective and commonly used medicines to treat various forms of arthritis and other rheumatic conditions. MTX was shown to improve signs and symptoms of RA, disease activity and function, to a similar degree as the tumor necrosis factor blockers, and it inhibits radiographic progression to a smaller degree than the antitumor necrosis factor agents. MTX is considered as the anchor drug among the disease-modifying antirheumatic agents, and it is internationally accepted as the first choice in the management of RA. This review was performed on the basis of a PubMed literature search looking at all publications on MTX and arthritis in 2008.
Recent findings: MTX seems to even prolong the life span of patients who tolerate the drug and have clinical benefit from this therapy; this may partly be explained by beneficial effects on cardiovascular mortality. The reason for this may well be the suppression of inflammation, but direct atheroprotective effects of MTX may also play a role. MTX is used as monotherapy and in combination with other disease-modifying antirheumatic agents or biologic agents such as the antitumor necrosis factor agents. The 'early' use of MTX within 5 years after disease onset is clearly associated with improved outcomes. The management of RA should include an early strong suppression of inflammation and continuously a tight control strategy. The pharmacodynamics and kinetics of MTX are still incompletely understood.
Summary: In this review, we especially cover the following themes: new clinical studies on the use of MTX in RA, the use of MTX in other rheumatic conditions, prediction of response to MTX, optimal dosage, MTX use in the elderly, the mechanism of action, the pharmacokinetics and the pharmacogenetics of MTX, the prevention of side effects, and the overall long-term safety.

Introduction

Methotrexate (MTX) has been used for the treatment of rheumatoid arthritis (RA) for about three decades now. Before Weinblatt et al.[1] published the first study in 1984, German rheumatologists such as one of the authors (R. Rau) had already started in the late seventies to treat severe patients on an individual basis with weekly low doses of a cytostatic drug that was not approved for RA therapy by the Food and Drug Administration (FDA) until 1988. Nowadays, it is one of the most effective and commonly used medicines to treat various forms of arthritis and other rheumatic conditions.

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