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The use of conventional disease-modifying anti-rheumatic drugs in established RA

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Conventional disease-modifying anti-rheumatic drugs (DMARDs) are the main tool to treat any form of rheumatoid arthritis (RA). Over the years, treatment strategies and use of DMARDs have changed. ‘Tight control’ and ‘treat-to-target’ are now the present paradigms. Combining DMARDs and adapting their dosages to obtain the best (clinical) result in individual RA patients with the least amount of medication has been and is studied worldwide. Literature results are mainly on early RA however, and they do not necessarily also apply to patients with established RA. Methotrexate (MTX) is the key conventional DMARD also for the treatment of established RA, and MTX often has to be combined with other DMARDs to reach low disease activity. However, there is lack of data on combination DMARD strategies and on how to treat best individual patients with established RA. In this review, we address these uncertainties and give an overview of available data.

Section snippets

Literature search

For this review, we used published meta-analyses, systematic reviews and randomised controlled trials (RCTs), if available. We based our search on ‘established RA’ and ‘conventional (synthetic) DMARDs’, including GCs and ‘DMARD strategies’.

Because of the lack of recent high-level literature addressing established RA, we have chosen to use literature addressing early RA as well where there is no high-graded literature available on established RA. Although the magnitude of effects and frequency

Currently available conventional DMARDs

As all available conventional DMARDs are used in all phases of RA, also established RA, we (in short) describe these drugs. The most common and dominant DMARD on the market is MTX [1], [10]. Among the available conventional DMARDs, MTX is also one of the most effective and best tolerated [26], [27], [28], [29]. Because of its favourable characteristics, MTX should be regarded as anchor DMARD; [23], [29], [30], [31], [32], [33], [34] it has several benefits over other DMARDs; see Box 1.

In

DMARD: monotherapy or combination therapy?

When starting to treat RA, treatment with a single DMARD as monotherapy remains a common first choice and is still considered by most rheumatologists the gold standard in treating DMARD-naive patients [15], [26], [28]. For established RA patients in developed countries however, it is not very common to be DMARD naive. If the wanted effect of the treatment is not reached with monotherapy in a preset time frame, combination therapy is initiated [33], [42]. Most established RA patients need

Combination strategies

There are different strategies to address combination DMARD therapy. A switch in strategies can be necessary if disease activity changes or if it flares. Although the approaches described below are mainly studied in early RA populations, they might also apply to the individual established RA patient; see Fig. 2.

Summary

In conclusion, for double and triple DMARD therapy we would recommend MTX as anchor drug, which can be combined with virtually any other (conventional) DMARD, but to restrict the combinations to those with evidence based efficacy and absence of excess toxicity, e.g. MTX-LEF or the MTX-HCQ-SSZ combination. Evidence based efficacy of conventional DMARD combinations excluding MTX is lacking. If the treatment target (low disease activity and preferentially remission) is not met, for their

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