Reach for the DMARDs
The Basics:
• In DMARD-naive patients, csDMARD monotherapy or combination therapy should be used, irrespective of the addition of glucocorticoids.
• Data on the efficacy of csDMARD combination therapy vs MTX monotherapy are conflicting. However, given that both approaches have supportive data, they are both included in the new guidelines as possible treatments. It is also pointed out that patient preferences and adverse event expectations should play a role in treatment selection.
• Data suggest that stepping up to bDMARD therapy from MTX monotherapy is more effective than moving to csDMARD combination therapy.
• Combination csDMARD therapy should in general include MTX.
Changes: The 2010 recommendation favored csDMARD monotherapy in DMARD-naive patients, irrespective of additional glucocorticoids, on the basis of the systematic literature reviews on which the guidelines were established. The new guideline weighs monotherapy and combination csDMARD options more equally, given recent data supporting the latter approach.
The Bottom Line: Here, some remarkable changes have been made. The use of combination therapy with conventional DMARDs -- and especially the triple therapy of MTX, sulfasalazine, and hydroxychloroquine, which was largely ignored in 2010 -- is here given as a reasonable option that is supported by several trials, including FIN-RACo, Swefot, TEAR, and RACAT. The guidelines stop short of recommending combination therapy for all patients, even though FIN-RACo, TEAR, and a recent trial (tREACH) all showed significantly better results with combination than with monotherapy. Avoidance of overtreating some patients still appears to be a very important consideration.
These recommendations do not include the first-line use of biologics, even though the previous recommendations did suggest that possibility for patients with severe disease. Clinical trials done with many biologics have demonstrated that the combination of a conventional DMARD (usually methotrexate) and biologic as first-line therapy is superior at the group level to a DMARD (MTX) alone. However, using such a combination might also lead to overtreatment in a lot of cases. Therefore, many experts feel that the option of early treatment with biologics (usually in combination with MTX) should be available, especially in patients with severe disease and a poor prognosis, but is to be used only in those cases. A separate discussion is whether combinations of conventional DMARDs or glucocorticoids could be equally effective (see the section "Consider Glucocorticoids," below).
Another remarkable and rather contentious change is the wording suggesting that the addition of biologics to MTX is more effective than the addition of conventional agents. This was indeed supported by the 1-year results of the Swefot trial and several secondary outcomes in RACAT. However, some experts believe that the advantage of biologics over conventional combinations is small and does not justify the greatly larger cost.