The last decade has seen numerous new treatments and treatment approaches that have literally transformed our way of thinking about rheumatoid arthritis (RA) and, more importantly, about the way we treat our patients. Major shifts in thinking have resulted in universal acceptance that early treatment with disease-modifying antirheumatic drugs (DMARDs) is important, that steroids indeed have DMARD activity, and that combinations of DMARDs can and should be used to treat patients with RA. Methotrexate remains the gold standard and is most often considered the drug of choice in the treatment of this disease, which has the potential to result in progressive disability in most patients. Methotrexate continues to demonstrate superior long-term efficacy compared with other conventional DMARDs29,38 and has recently been shown to be equivalent to etanercept when used to treat early RA.6 Despite its success as monotherapy, however, approaches that combine methotrexate with other DMARDs are now used for treatment of the growing number of patients with RA who fail to achieve disease control with methotrexate alone.19 A recent survey of US rheumatologists revealed that 99 used combination DMARDs to treat an estimated 24 of all patients. Another recent survey16 has shown that almost half of rheumatologists in the United States are currently using combinations of DMARDs to treat over 30 of their patients; this number has gone up dramatically from less than 15 just 4 years ago. Recently, three different studies on early RA have demonstrated the superiority of combinations of DMARDs over monotherapy (reviewed in the article by Boers in this issue).1,2,18 Other approaches using combination therapy include methotrexate plus biologic agents that decrease tumor necrosis factor (TNF) activity. Clinical studies of such agents (infliximab, etanercept) in patients who had less than optimal responses to methotrexate have shown each of them to be more effective than placebo when added to the baseline methotrexate (reviewed in the article by Keystone in this issue).15,36 With few exceptions, all the clinical trials that have demonstrated success of combination therapy for RA have included methotrexate as part of the combination. Methotrexate thus is currently the cornerstone of combination therapy.13 Studies are currently underway to determine if leflunomide might be an option to replace methotrexate in some combinations. The combination of methotrexate with DMARDs or with biologic agents offers the potential for four possible outcomes. First, efficacy or toxicity of the combination therapy may be less favorable than with single-drug therapy. This is of particular concern with regard to toxicity issues such as the potential for additive liver blood test abnormalities with the combination of methotrexate and leflunomide.35 Second, efficacy or toxicity may be no different than with single-drug therapy. Third, efficacy or toxicity may be additive; this outcome of additive efficacy could represent either a true additive effect on each patient, the sum of two subpopulations of patients (each of which is responsive to one of the two drugs), or, more likely, a combination of these two situations. Finally (what we are all hoping for), the efficacy of combinations of DMARDs may be synergistic without increasing toxicity; in other words, the response is clearly greater in magnitude or frequency than would have been expected with the individual drugs added together. This situation is further complicated, because most trials are not designed in a way that allows us to answer these questions directly.

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{{Explor lien
   |wiki=    Sante
   |area=    ChloroquineV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     ISTEX:D04F11423AF80F59FF11BF8A5704F3F9D793D19E
   |texte=   COMBINATIONS OF CONVENTIONAL DISEASE-MODIFYING ANTIRHEUMATIC DRUGS
}}