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RA Prevention and Treatment

CME

Rheumatoid Arthritis Prevention and Treatment: My Top Studies From EULAR 2020

Physicians: Maximum of 0.25 AMA PRA Category 1 Credit™

Released: July 16, 2020

Expiration: July 15, 2021

Paul Emery
Paul Emery, MA, MD, FRCP
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EULAR recently hosted a virtual version of its annual congress of rheumatology, and we saw numerous new studies that promise to expand our understanding of rheumatoid arthritis (RA) and improve efforts at earlier detection and intervention.

Here’s my take on some of the most important findings in prevention and treatment.

Progression and Prevention
In thinking about the natural history of RA, we now have an established concept of the continuum between genetic risk, environmental risk, and the development of clinical disease. It is clear that before the development of inflammatory arthritis, systemic autoimmunity occurs when autoantibodies are detectable in the serum, namely anticitrullinated protein antibodies (ACPA), often measured by anti–cyclic citrullinated peptide (CCP). At EULAR 2020, there were numerous virtual abstracts that, I think, put this continuum and the potential implications for prevention at the forefront of current research.

Gut Microbiome
Starting with the initiating mucosal event that leads to autoimmunity, Tong and colleagues presented an interesting study in which they compared the diversity of gut microbiome samples from healthy controls, patients who were considered pre-RA (classified by anti-CCP–positive serum), and patients with diagnosed RA. They found a decreased diversity of intestinal microbes in pre-RA patients vs healthy controls and showed that the microbial signatures of pre-RA patients was intermediate between those of healthy controls and patients with RA.

In a separate and noteworthy proof-of-principle experiment, they performed fecal transplants in a mouse model of RA and demonstrated that fecal transplants from this pre-RA population disrupted gut permeability and promoted joint redness and inflammation significantly more than fecal transplants from healthy controls.

Periodontal Disease
Similarly, Mankia and colleagues performed a prospective cohort study assessing the relationship between periodontal disease and progression to RA among at-risk individuals with detectable anti-CCP but no clinical synovitis. They found that the presence and severity of periodontal disease was predictive of progression to RA. These interesting results suggest that intervening with dental hygiene may be one way to reduce or retard progression to RA in at-risk patients.

Predicting Progression
When caring for at-risk patients, risk models are useful for predicting both the likelihood and timing of developing arthritis. Duquenne and colleagues presented new data validating a preexisting primary care model and a secondary care model. Among 394 patients with anti-CCP but no clinical synovitis, they confirmed that a high titer of autoantibodies, early morning stiffness, and pain localized to the hands or feet are predictive of progression in the primary care model. In the secondary care model, predictive markers included all of those confirmed in the primary care setting plus the genetic marker from the class II–shared epitope and the presence of Power Doppler signal. Thus, we have risk-prediction models for both primary and secondary care.

Expanding on the utility of ultrasound, the same group reported, in a separate abstract, that the number of Power Doppler–positive joints in at-risk ACPA-positive patients was correlated with their risk for progression to inflammatory arthritis. Indeed, those with ≥ 4 positive joints were 6 times more likely to develop inflammatory arthritis during a median of 96 weeks of follow-up. In a similar vein, Di Matteo and colleagues found that the presence of an ultrasound erosion at the V metatarsophalangeal joints in at-risk patients was highly predictive of progression to clinical arthritis.

Clearly, the data on ultrasound demonstrate that we have a relatively straightforward screening test that can improve our identification and management of at-risk patients. Moreover, these findings raise the question of whether we should consider subclinical disease with the presence of imaging-found synovitis as being a separate disease.

In favor of this notion was a study looking at patient-reported outcomes in the weeks before developing clinical arthritis. The authors found highly significant changes in general health, global pain, fatigue, and function, suggesting that patients experience a distinct disease—one that is indicative of imminent progression to clinical arthritis. Clinical arthritis, therefore, may be viewed as a rather late development, and we must begin to assess and intervene at earlier stages along the continuum of disease. Further support of this concept came from Garcia-Montoya and colleagues, who reported that at-risk patients who progress to inflammatory arthritis have higher levels of interferon-stimulated gene expression prior to clinical synovitis and ultrasound signal.

Emerging Therapy Trends: Early Disease
Reinforcing the importance of early identification and intervention in patients with RA, Niemantsverdriet and colleagues compared clinical outcomes among patients who were referred to a rheumatologist within 6 weeks of symptom onset vs later than 6 weeks. Those who were referred within 6 weeks had a higher chance of achieving sustained disease-modifying antirheumatic drug (DMARD)–free remission, which is a fantastic endpoint akin to a temporary cure; it is an outcome we can only wish for in the future.

These data highlight the importance of early intervention. We should not allow patients to endure years without optimal treatment.

My particular bias is that if we are using biologics, we should be using them early to get this sort of profound remission.

Emerging Therapy Trends: Long-standing Disease
Remission is the outcome we all want. And we are achieving it increasingly frequently. But what about remission in patients with long-standing disease? The guidelines for how to treat patients in remission or how to withdraw drugs after remission is still uncertain. There are many studies that are hard to resolve.

One study at EULAR by Lillegraven and colleagues looked at patients with long-standing RA who had achieved sustained remission with anti-TNF biologic agents and conventional synthetic DMARDs. It was a very simple message: They found that after tapering and withdrawal of the anti-TNF biologic, flares increased to almost 60% at the end of the year.

However, the good news is that when they reinstated therapy, nearly all of the patients regained control.

To me, this makes it increasingly clear that in patients with long-standing disease who are in remission on combination TNF and conventional synthetic DMARD, you may be able to taper and reduce the frequency or the dose of the biologic, but it is very unlikely that you will discontinue it completely. And if you are stopping, you must have a rapid access to the biologic because it is important to be able to reinstate the treatment quickly.

My recommendation for a patient with long-standing disease is to be very cautious—if the patient is doing well, you could actually taper but do it very slowly and watch for a considerable amount of time. Be very cautious about stopping a biologic.

Hydroxychloroquine Safety
Another treatment that is become very newsworthy is hydroxychloroquine. There has been a lot of disturbing information for our patients about the toxicity of hydroxychloroquine, which—in this era of COVID-19—has gone from the hero to the villain. During studies in COVID-19, where it was used with azithromycin or in high dose, hydroxychloroquine was painted as a horrible drug that causes death and heart failure.

At EULAR, data from Sorour and colleagues showed that there was no association with heart failure among patients with RA receiving hydroxychloroquine in contrast to the data from the COVID-19 studies.

The rheumatology experience is very clear. Our patients tolerate the doses we give extremely well, and we do not mix hydroxychloroquine with drugs that have been associated with arrythmia. The most important message for our patients with RA is not to stop the hydroxychloroquine.

What we do know is that hydroxychloroquine probably does not treat COVID-19, but what is still uncertain is whether it acts as a preventative.

Your Thoughts?
Which new data from EULAR 2020 will most influence your management of patients with RA? Join the discussion by posting a comment below. For more coverage of RA from the virtual meeting, download focused Capsule Summaries of key studies and use the slides in your own presentations.

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