Original articleOptimizing methotrexate therapy in rheumatoid arthritis: A systematic literature review
Introduction
The introduction of biotherapies over the last few years is perceived as a breakthrough in the treatment of inflammatory joint diseases. Nevertheless, methotrexate (MTX) remains the cornerstone of disease-modifying treatment in patients with rheumatoid arthritis (RA) [1], [2]. Recent national and international recommendations support the use of MTX as the first-line disease-modifying antirheumatic drug (DMARD) for RA, based on its substantial effectiveness, good safety profile, and low cost [3], [4], [5], [6], [7]. MTX is also widely used in combination with other medications, most notably biotherapies, to increase their therapeutic effect [8], [9], [10]. However, considerable variability exists across rheumatologists regarding the MTX starting dosage, dosage increment size, interval between increments, and route of administration. The recommendations issued by the French High Health Authority for the management of established RA suggest a number of gray areas regarding the modalities of MTX use. In published studies of first-line biologic therapy for RA, over one-third of patients achieved a clinical remission in the control groups treated with MTX alone but another third had no treatment response [8], [9], [10], [11]. The absence of a response may indicate either a primary lack of efficacy or a suboptimal MTX regimen [12]. The objective of this work was to describe the means of optimizing MTX therapy in RA in daily clinical practice, based on a systematic literature review.
Section snippets
Definitions of topics of interest
A scientific committee composed of French rheumatologists working in teaching hospitals used a Delphi procedure to select topics of interest. Four topics were selected: the MTX starting dosage, the size of the dosage increments and interval between increments, the maximum dosage, and the route of administration at treatment initiation and during maintenance therapy.
Literature search
We searched the Medline, Embase, and Cochrane Central databases for articles published until May 2009, with no date limits. The
Results
Fig. 1 shows the flowchart of the articles. Our literature search retrieved 519 articles, among which 26 were preselected based on the titles and abstracts. Of these, nine were selected based on the full-length text [16], [17], [18], [19], [20], [21], [22], [23], [24]. In addition, we included two abstracts from recent meetings, of which one reported an a posteriori analysis of a previously published study [25] and the other supplied additional information on the dosage increase schedule [26].
Discussion
This systematic revue deals with the optimization of MTX use for patients with RA in daily clinical practice. An intensive strategy (consisting in high starting dosage [18], [21] followed by monthly increments of 5 mg [23]) is associated with a higher rate of minor adverse events, most notably involving the gastrointestinal tract, compared to the traditional use of MTX [18], [21], [23]. The intensive strategy is warranted in patients with early RA to take advantage of the window of opportunity
Disclosure of interest
This work was done as part of the 6th Rheumatology Expert Meetings organized with institutional support from Abbott France. Abbott was not involved in any way in the project. The authors have no financial interest related to the topic of the study. Thus, the authors have no conflict of interest to declare.
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The French High Health Authority recommends a maximum dosage of 25 mg/week with appropriate adjustments based on clinical effectiveness and tolerance.