When I Consider Biologic or Targeted Synthetic DMARD Monotherapy for Patients With Rheumatoid Arthritis

Roy Fleischmann, MD

Clinical Professor of Medicine
Department of Medicine
University of Texas Southwestern Medical Center
Metroplex Clinical Research Center
Rheumatology Associates
Dallas, Texas

Roy Fleischmann, MD, has disclosed that he has received consulting fees and/or funds for research support from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Pfizer, Roche, and Sanofi Genzyme.

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Released: June 8, 2018

Biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) now have a central role in treating patients with rheumatoid arthritis. Although these agents are often used in combination with the conventional synthetic DMARD (csDMARD) methotrexate and are generally more effective when combined with this agent, there are settings in which bDMARD or tsDMARD monotherapy may be appropriately considered. Herein, I examine these settings.

Initial Inadequate Response to a csDMARD With Improvement After Addition of a bDMARD or tsDMARD
A scenario in which bDMARD or tsDMARD monotherapy may be considered is that in which a patient has experienced an inadequate response to csDMARD therapy and subsequently demonstrated a marked improvement with the addition of a bDMARD or tsDMARD. As discussed earlier, the combination of methotrexate with bDMARDs or tsDMARDs is generally more effective than bDMARD or tsDMARD therapy alone—with the exception of the IL-6 inhibitor tocilizumab, which may be as effective when used as monotherapy—and this additive strategy is endorsed by both the American College of Rheumatology and European League Against Rheumatism guidelines.

However, for patients who achieve long-standing remission with the addition of a bDMARD or tsDMARD, tapering of the csDMARD could be considered—especially when it has been combined with specific bDMARDs or tsDMARDs—and discontinuation may be possible if the patient maintains response. Numerous studies have found that following discontinuation of a csDMARD in patients simultaneously treated with a TNF inhibitor, only a limited number will maintain response. By contrast, most patients undergoing tapering of a csDMARD during cotreatment with an IL-6 inhibitor (eg, tocilizumab or sarilumab) or JAK inhibitor (eg, tofacitinib) will maintain response with monotherapy.

csDMARD Intolerance, Contraindication, or Patient Preference for Non-csDMARD Therapy
Further scenarios in which treatment with bDMARD or tsDMARD monotherapy would be appropriate are those of patients who cannot or do not want to take a csDMARD. For example, methotrexate and leflunomide affect the liver. Hence, in a patient with elevated liver function tests suggestive of liver disease, monotherapy with an IL-6 or JAK inhibitor (vs other bDMARDs) may be considered. Rarely, a patient may also refuse treatment with a csDMARD based on what they have heard about the potential adverse events of these medications. This would be an instance in which one might consider starting a patient on bDMARD or tsDMARD monotherapy.

Tapering and possible discontinuation of a csDMARD that has been combined with a bDMARD or tsDMARD can also be considered if a patient develops intolerance to the csDMARD (eg, complaints such as nausea or hair loss) or significant laboratory abnormalities or if a patient strongly prefers to take a single medication over combination therapy. This latter circumstance occurs not infrequently in my experience. Whatever the cause, tapering should occur over a reasonable period to allow for detection of any disease flare.

A much less common scenario for consideration of bDMARD or tsDMARD monotherapy would be that of a newly diagnosed woman who wants to become pregnant within a relatively short time, such as 1 year. In general, it takes methotrexate 3-6 months to become fully active, and this agent should be discontinued at least 3 months before a woman becomes pregnant. Thus, use of methotrexate would mean a lengthy induction before disease amelioration that would need to be followed by a significant discontinuation period before pregnancy could even be considered. By contrast, JAK inhibitors have a very short half-life, and it is conceivable that a response may be evident within weeks. This response could be maintained until the patient decides that she wants to become pregnant. Then, following discontinuation of the JAK inhibitor for 1 or 2 menstrual cycles, pregnancy would be a viable option. I have occasionally used this approach in clinical practice.

Your Thoughts
Overall, it is rare to start a bDMARD or tsDMARD as first-line monotherapy other than in very specific instances in which patient safety dictates such a choice. It is much more common to think about using monotherapy in patients who have achieved sustained remission while receiving a bDMARD or tsDMARD plus a csDMARD. When do you recommend bDMARD or tsDMARD monotherapy for your patients? I invite you to join this conversation in the comments section below or by answering the polling question on your screen.

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