New Efforts to Define Difficult-to-Treat RA
An ongoing issue faced by many rheumatologists in clinical practice is that a number of patients living with RA remain symptomatic despite a variety of existing therapy options. Many of these patients would be classified as having difficult-to-treat RA according to EULAR criteria1 and represent a population facing an unmet need within the RA field. I am delighted to have been a member of the EULAR task force on difficult-to-treat RA, a multidisciplinary committee that worked to develop recommendations for managing patients with difficult-to-treat RA.1 Our first step in this mission was to define difficult-to-treat RA more clearly. Members of the task force, and many other researchers, presented on and discussed our recently published definition criteria1 and other considerations related to difficult-to-treat RA during several EULAR 2021 sessions.2-4 I was excited to see a number of presentations that referred to our EULAR task force work, a few of which I discuss below.
Many colleagues and I presented on the high prevalence of comorbidities in RA,3,4 making the case that comorbidities and difficult-to-treat RA are “different sides of the same coin.”3 Comorbidities can accelerate inflammation, limit treatment options, and influence disease measures, yet they tend to be neglected in RA treatment recommendations. A Greek study using the EULAR criteria found that increased comorbidities at the start of treatment are an independent factor of reduced response to therapy at 6 months and, ultimately, classification as difficult to treat.5 It is important to identify and address comorbidities early, especially for patients with difficult-to-treat RA.
A poster by Hirano et al presented at EULAR 2021 used a modification of the EULAR task force definition to assess incidence rates of difficult-to-treat RA from a real-world clinical practice in Japan. This study found that ≈9% of 363 patients receiving treatment with b/tsDMARDs had difficult-to-treat RA. These patients tended to be older, had a long disease duration, were receiving concomitant methotrexate and/or prednisone, and had higher disease activity at the time of b/tsDMARD initiation.6 We are hopeful that our newly established definition of difficult-to-treat RA will enable more accurate incidence rate estimations in the future, which will assist in providing a better understanding of the scope of this disease.
The EULAR task force has defined difficult-to-treat RA and has also worked toward providing guidance on how to manage difficult-to-treat RA. Although the latter is in development, other researchers have used the EULAR definition of difficult-to-treat RA to frame their management recommendations, some of which were presented at EULAR 2021.
The additional complications of treating patients with rheumatologic diseases during the COVID-19 pandemic were reflected in a study from Italy, with results suggesting that telehealth was a feasible strategy in the management of patients experiencing difficult-to-treat RA.7
Another study found that JAK inhibitors were effective in treating difficult-to-treat RA in patients who had inadequate response to ≥2 bDMARDs, regardless of patient background or prior number of bDMARDs. Retention rates of JAK inhibitors ranged from 51% to 66% at 1 year, although patient numbers in this retrospective study were low.8
Our understanding of difficult-to-treat RA is continuing to evolve, and much remains to be done to determine the best treatment strategies for patients. I am excited to be part of this work. In the meantime, it is important to maintain a patient-centric, holistic approach that addresses all relevant patient- and disease-related factors, including comorbidities, to find an optimal treatment for each patient.
1. Nagy G, et al. Ann Rheum Dis. 2021;80:31-35.
2. EULAR 2021. Standing Committee on Clinical Affairs session. June 3, 2021.
3. EULAR 2021. Multi-disciplinary care: the new era of rheumatology session. June 2, 2021.
4. EULAR 2021. Difficult-to-treat RA session. June 4, 2021.
5. Flouri I, et al. EULAR 2021. Oral OP0299.
6. Hirano Y, et al. EULAR 2021. Poster 0450.
7. Ingegnoli F, et al. EULAR 2021. Poster 1182.
8. Kamiya M, et al. EULAR 2021. Poster 0088.
bDMARDs, biologic disease-modifying antirheumatic drugs; EULAR, European League Against Rheumatism; RA, rheumatoid arthritis; tsDMARDs, targeted synthetic disease-modifying antirheumatic drugs.
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