Several guidelines have recommended using a combination of conventional synthetic DMARDs (csDMARDs), including MTX, as initial treatment. [See sidebar, below, for a description of the acronyms used to distinguish the varying types of DMARDs.] However, Dr. Smolen says current evidence also supports a strong recommendation for combining a csDMARD with glucocorticoids. He underscores that the data show no advantage of adding another csDMARD (e.g., sulfasalazine [SSZ] or leflunomide or SSZ plus hydroxychloroqauine), and that combinations of csDMARDs show more frequent adverse events than when combining MTX with a short course of glucocorticoids.
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Explore This IssueJuly 2017
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“Some colleagues do not like the fact that we omitted combination csDMARDs,” says Dr. Smolen, “but we provide the evidence for doing this.”
Dr. Bykerk also notes that this recommendation was not without controversy and highlights “the need for more current studies of combination DMARDs, particularly in comparison with higher dose MTX and subcutaneous MTX.”
For second-line treatment for patients who do not reach their target goal of remission or low disease activity, the new guideline recommends stratification by risk factors of rapid damage progression. “If these risk factors are absent, another csDMARD strategy can be used,” he says.
However, for patients with poor prognostic factors, he says any biologic DMARD can be used, as well as a Janus kinase (JAK) inhibitor. The use of a JAK inhibitor as an alternative to a biologic DMARD in this context is now recommended on the basis of new long-term data on JAK inhibitors for second-line therapy, he says.
Of note is the recommendation for combining biologic DMARDs and JAK inhibitors with MTX or other csDMARDs, based on evidence showing that the combination of these agents appears generally more efficacious than monotherapies.
Dr. Smolen says this recommendation, too, may be controversial for some rheumatologists. “Some rheumatologists would have preferred that we recommend some biologics, such as tocilizumab and Jakinibs, for monotherapy,” he says. “But again, we have sufficient evidence that combination conveys better outcomes.”
As to the recommendation for tapering treatment for patients who achieve persistent remission, Dr. Bykerk emphasizes that the guidelines stress the importance of tapering slowly and following a “reverse treat to target” approach in which any reduction will still ensure no loss of disease control. “It is too early to be prescriptive as to what order therapies should be tapered,” she says. “The only exception to this was that steroid [use] should be the first therapy tapered and that their use, in fact, should always be considered short term.”
The ACR 2015 Guideline
The 2016 EULAR guideline and 2015 ACR guideline are based on similar treat-to-target treatment strategies.