expert roundtables

Unmet Needs in the Treatment of Rheumatoid Arthritis

by Leonard H. Calabrese, DO, Stanley B. Cohen, MD, Alan L. Epstein, MD, Daniel E. Furst, MD

Overview

Experts in rheumatoid arthritis (RA) and their patients are grateful for advances attributable to the anti–tumor necrosis factor (TNF) agents; however, they also identify challenges in achieving deep remissions in a significant subset of patients with RA, despite the availability of anti-TNF therapy. Accordingly, panelists critically evaluate current paradigms and practice patterns in RA, wherein nonbiologic, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are initiated, followed very quickly by biologic DMARDs in those patients with moderate to severe disease who have had an inadequate response to csDMARDs.

Q: What are the challenges and unmet needs that affect the care of patients with RA who have had an inadequate response to therapy?

Leonard H. Calabrese, DO

Professor of Medicine
RJ Fasenmyer Chair of Clinical Immunology
Director, RJ Fasenmyer Center for Clinical Immunology
Vice Chair, Department of Rheumatic and Immunologic Diseases
Cleveland Clinic Foundation
Cleveland, OH

“About one-third of patients do not have the gratifying response to anti-TNF therapy that is more typical of the remainder of the population.”

Leonard H. Calabrese, DO

There are numerous unmet needs in RA—diagnostic needs, the need for biomarkers, staging needs, and needs in therapeutic areas. Focusing on the more difficult-to-treat patients, it is true that, while we have been blessed to have had anti-TNF agents for 2 decades, it seems that, no matter how these agents are used and regardless of the therapeutic sequence, it can be a challenge to achieve a deep remission, particularly for those who have established disease. About one-third of patients do not have the gratifying response to anti-TNF therapy that is more typical of the remainder of the population.

Alan L. Epstein, MD

Clinical Professor of Medicine
University of Pennsylvania School of Medicine
Attending Physician and Chief of Rheumatology
Pennsylvania Hospital
Philadelphia, PA

“I think that there is a habit of initiating an anti-TNF agent in a patient with an inadequate response to methotrexate.”

Alan L. Epstein, MD

Anti-TNF agents have been around for about 20 years; rituximab and abatacept were introduced for RA treatment in 2006 and 2005, respectively, and the interleukin (IL)-6 receptor inhibitor tocilizumab was approved by the US Food and Drug Administration (FDA) for RA in 2010—so, these agents have been around for a long time.

anti-TNF therapy Graph

If we examine practice patterns amongst rheumatologists across the country, and, indeed, around the world, I think that there is a habit of initiating an anti-TNF agent in a patient with an inadequate response to methotrexate. I believe that this, in large measure, is because anti-TNF agents were the first group of biologic drugs available, and we have had roughly 20 years of experience with using them. There is a general comfort level with them, and so, clinicians tend to go to this therapeutic class ahead of those with other mechanisms of action. However, wouldn’t it be nice to be able to predict which patients will do best on which drug? And, I’d perhaps add, at which point in the patient’s disease?

Stanley B. Cohen, MD

Clinical Professor of Medicine
UT Southwestern Medical Center
Co-Director, Division of Rheumatology
Presbyterian Hospital
Dallas Dallas, TX

“It would be great to have some kind of treatment biomarker that would help us to discriminate among patients (ie, to predict those who are going to be inadequate responders to TNF and those who may be inadequate responders to other biologics).”

Stanley B. Cohen, MD

Many of us who are older can recall the days prior to the clinical use of biologics, and so, we recognize that, today, we can help patients in ways that were not possible back then. We know the current treatment paradigm, based not only on recommendations from the American College of Rheumatology (ACR) but also from the European League Against Rheumatism (EULAR), whereby we use nonbiologic csDMARDs first, followed very quickly by biologic DMARDs in those patients who have an inadequate response. It would be great to have some kind of treatment biomarker that would help us to discriminate among patients (ie, to predict those who are going to be inadequate responders to TNF and those who may be inadequate responders to other biologics). Another point is that, even 20 years later, we still have questions and issues that arise about the safety of these drugs in patients with multiple comorbidities. And, in rheumatology, we frequently have long arguments or discussions about clinically significant risk versus absolute risk; patients still come in to see us expressing reservations about taking these drugs in cases where, clearly, the safety parameters have been well delineated.

Daniel E. Furst, MD

Professor of Medicine, University of California (emeritus)
UCLA Medical Center, Department of Medicine
Division of Rheumatology
UCLA Medical Center
Los Angeles, CA

“Another unmet need is that of measurement (ie, the use of quantitative RA measurement tools). Unfortunately, the uptake of these assessment tools in the real world is not as good as we would like.”

Daniel E. Furst, MD

I agree with what has been said. I would add that another unmet need is that of measurement (ie, the use of quantitative RA measurement tools). Unfortunately, the uptake of these assessment tools in the real world is not as good as we would like. Even with the Routine Assessment of Patient Index Data 3 (RAPID3), which should be an absolute “no-brainer” for the physician, the data suggest that uptake has only been around 30%. So, we’ve got a ways to go.

References

Chua JR, Castrejon I, Pincus T. Assessment of pain and other patient symptoms in routine clinical care as quantitative, standardised, “scientific” data. Clin Exp Rheumatol. 2017;35 Suppl 107(5):13-20.

Cuppen BV, Welsing PM, Sprengers JJ, et al. Personalized biological treatment for rheumatoid arthritis: a systematic review with a focus on clinical applicability. Rheumatology (Oxford). 2016;55(5):826-839.

Curtis JR, Chen L, Danila MI, Saag KG, Parham KL, Cush JJ. Routine use of quantitative disease activity measurements among US rheumatologists: implications for treat-to-target management strategies in rheumatoid arthritis. J Rheumatol. 2018;45(1):40-44.

Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26.

Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;4:18001.

Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017:76(6):960-977.

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