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Even in the current era of biological targeted therapies, methotrexate (MTX) remains the initial preferred antirheumatic drug and is widely prescribed for patients with rheumatoid arthritis (RA). The combination of its perceived efficacy, acceptable safety profile and low cost, as well as decades of clinical experience with its use that have been accumulated by current and previous generations of rheumatologists, make MTX the cornerstone of treatment for RA and the anchor drug for combination with each of the newer biological agents.
Four papers in this journal1–4 provide general guidance for the use of MTX, its optimal dose and route of administration and its potential toxicity (see articles on pages 1086, 1094, 1100 and 1105). This “3E Initiative,” supported by an unrestricted educational grant from Abbott, began with an extensive systematic literature review (Evidence) that was discussed by each of 17 national scientific committees (Expertise). These national groups combined to form a broad international panel of experts who shared (Exchange) the individual national recommendations. While acknowledging changes in MTX use over time and in different geographical regions, the authors propose consensus guidelines for the use of MTX to manage patients with RA.
Of the “Evidence” accumulated by the authors’ search of the medical literature, nearly half (9/19) of the studies of MTX use that were included in their meta-analysis had been published during the last decade of the 20th century.4 The authors acknowledge that, during this era, MTX was prescribed at lower doses than are currently used. Also, folic acid supplementation was not administered as systematically and MTX doses were escalated less rapidly than is the current custom. In addition, the disease-modifying antirheumatic drugs (DMARDs) with which MTX was combined in these studies included DMARDs not commonly used in current clinical practice (such as intramuscular …
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