Current and Future Role of Methotrexate in the Therapeutic Armamentarium for Rheumatoid Arthritis

Evripidis Kaltsonoudis; Charalampos Papagoras; Alexandros A Drosos

Disclosures

Int J Clin Rheumatol. 2012;7(2):179-189. 

In This Article

Abstract and Introduction

Abstract

Methotrexate (MTX) has been used for rheumatoid arthritis (RA) treatment since 1980. It is the most common effective disease-modifying antirheumatic drug (DMARD) for RA, and is considered to be the anchor drug, to which other DMARDs or biological agents are added to, in order to achieve an optimal therapeutic effect. MTX improves signs and symptoms to a similar degree as anti-TNF agents. However, it seems to inhibit radiographic progression less effectively than anti-TNF agents. The appropriate route of administration and optimal dose should be individualized depending on the profile and response of the patient. It seems to be one of the safest DMARDs, while there is evidence that patients treated with MTX have lower mortality, especially due to cardiovascular causes. Currently, there is no reliable way to predict which patients will respond to treatment with MTX, and who will experience side effects, the answer to which remains to be clarified.

Introduction

Methotrexate (MTX) is currently the most frequently used disease-modifying antirheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA). Since it was first administered to RA patients, its use has become more and more widespread and the doses applied have gradually increased from initial lower doses to the levels that are considered effective and safe today.

The development of MTX as a therapy for RA initially evolved from isolated case reports followed by uncontrolled case series, placebo-controlled studies and, finally, randomized double-blind active comparator studies.[1–3] The importance of MTX in the therapeutic armamentarium for RA has also been emphasized over the past few decades by the increased therapeutic efficacy observed, when synthetic or biologic DMARDs are added to MTX.[1]

The importance of MTX in earlier and more aggressive management of RA patients cannot be overemphasized. MTX is one of the most flexible antirheumatic drugs, given that it can be used as a monotherapy, in combination with glucocorticoids, other synthetic DMARDs, and biologic agents to enhance their efficacy. The safety profile of the weekly low doses used for RA treatment has been studied for over 25 years with very few clinically relevant adverse events. Courses of MTX show some of the longest continuation rates reported in clinical medicine, owing to both its effectiveness and safety. This safety profile makes MTX one of the safest drugs available for the treatment of RA, as well as other forms of chronic inflammatory arthritis.[4,5]

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