Newer Agents as Monotherapy for Patients With RA

Jasvinder Singh, MD, MPH

Professor of Medicine and Epidemiology
Division of Rheumatology
Department of Medicine
University of Alabama at Birmingham
Staff Physician
Birmingham VA Medical Center
Staff Rheumatologist
The Kirklin Clinic
Birmingham, Alabama


Jasvinder Singh, MD, MPH, has disclosed that he has received consulting fees from Crealta/Horizon and Fidia.


View ClinicalThoughts from this Author

Released: August 2, 2018

There have been several additions to the rheumatoid arthritis (RA) treatment armamentarium in recent years, including the JAK inhibitors baricitinib and tofacitinib and the IL-6 receptor antagonists sarilumab and tocilizumab. Although these agents are generally recommended for use in combination with methotrexate or other conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) for patients who have had an inadequate response to a csDMARD or biologic (b) DMARD, there are scenarios in which these newer agents might be used as monotherapy. In this commentary, I present a case illustrating the type of patient I would consider for monotherapy with a newer bDMARD or targeted synthetic (ts) DMARD and discuss some of the data assessing newer agents as monotherapy for patients with RA.

When to Consider Monotherapy: Case Patient
A 48-year-old woman was diagnosed with moderately active RA 7 months ago and started on methotrexate. At her most recent clinic visit, her disease activity remained moderate and she reported low level nausea that she associated with methotrexate. She wonders if she should change her treatment but expresses a desire to keep her pill burden as low as possible.

According to the ACR guidelines, options for a patient who has demonstrated an inadequate response to methotrexate would include the addition of 1 or more csDMARDs (eg, sulfasalazine) to methotrexate or treatment with a bDMARD or tsDMARD, with or without methotrexate. The ACR guidelines recommend that biologic therapy be combined with methotrexate when possible for patients who have moderate/high disease activity despite csDMARD monotherapy.

For this patient, 2 factors might suggest the consideration of bDMARD or tsDMARD as monotherapy: First, the patient experienced nausea with methotrexate, and second, the patient does not wish to have a considerable pill burden. In my practice, these scenarios are not rare. I would certainly consider discussing monotherapy with this patient.

Efficacy of Newer Agents as Monotherapy
What is the evidence supporting the use of newer agents as monotherapy for patients who have experienced csDMARD failure? Data continue to emerge, as shown in the table below. It should be noted that TNF inhibitors and newer agents are generally more effective when combined with methotrexate, hence the recommendation by the ACR that methotrexate remain part of a treatment regimen for patients who have failed initial monotherapy with this agent, if possible. I generally do not consider bDMARD or tsDMARD monotherapy in the first-line setting, but based on the evidence, I will consider it for certain patients who have failed csDMARD therapy.

Table. Selected Phase III/IV Trials of Assessing Monotherapy With Newer bDMARDs/tsDMARDs for Patients With RA
Close

As mentioned above, the ACR guidelines recommend that biologic therapy be combined with methotrexate when possible for patients who have moderate/high disease activity despite csDMARD monotherapy. However, as discussed above, some patients might desire the omission of methotrexate from their treatment regimen due to a documented adverse event, personal preferences, or a desire for a lower pill burden. In practice, a clinician must weigh patient factors and preferences when determining a treatment course with a patient. As stated earlier, some of my patients have stated that they would prefer a lower pill burden. Some may even be willing to sacrifice a small degree of efficacy to avoid having to continue taking multiple medications. However, such discussions have to be detailed and supported by available data regarding short- and long-term outcomes, making sure that patients understand these complex concepts. This is usually a discussion that spans several visits, and requires the use of simple numbers, pie charts, and examples from a patient’s daily life.

Final Thoughts
Selecting a therapeutic course for patients with RA—particularly those who have failed csDMARD or bDMARD therapy—can be challenging. In general, patients who have failed csDMARD therapy should maintain methotrexate when possible; however, as described above, bDMARD or tsDMARD monotherapy can be considered in some patient scenarios, most notably for patients who have demonstrated an inadequate response or intolerance to methotrexate or would prefer fewer pills or injections. This is often a personal decision involving both the patient and clinician.

I have found the evidence that continues to emerge supporting the use of monotherapy in certain clinical scenarios quite valuable in my practice; I am now able to tell patients that there is quality data supporting monotherapy. I also think that more robust data of direct head-to-head comparisons of monotherapy regimens, which include longer-term outcomes, are needed.

Have you recommended newer agents as monotherapy in your practice? For what type of patient did you recommend this option? I encourage you to join the conversation in the comments section below or by answering the polling question on your screen.

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