ACR 2021: 11 New Things to Know About Rheumatoid Arthritis

At the American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting this year — ACR Convergence 2021 — more than 16,500 attendees and 600 speakers from more than 100 countries gathered virtually to share the latest research and address the most pressing issues for people living with rheumatic disease.

The CreakyJoints team soaked it all in — listening, watching, and learning so we could bring you the most relevant information to ensure you know what you need to better manage your condition and get better care.

We combed through hundreds of studies, attended sessions from top RA experts, and asked our team of patient and physician advisors to share the rheumatoid arthritis updates they deemed most important for patients.

The result: Our curated, patient-friendly guide to rheumatoid arthritis research and trends from ACR 2021. For more research breakthroughs from ACR 2021, check out our main guide: 100+ Arthritis & Rheumatic Disease Updates You Need to Know.

1. The biologic abatacept (Orencia) may help reverse early-stage rheumatoid arthritis

Rheumatoid arthritis doesn’t strike overnight. Rather, it’s thought to progress over time, starting with a “pre-clinical” stage where people have certain antibodies associated with RA (such as anti-cyclic citrullinated protein, or anti-CCP) and mild symptoms like some joint pain. Can intervening at this stage help prevent progression to RA? Abatacept (Orencia) is a biologic drug that blocks T cells in the immune system. T cells can play a role in triggering autoimmune inflammatory diseases like RA, so interventions that stop this process may help prevent RA.

At ACR, European researchers shared the results from a randomized controlled trial of 100 patients at risk of developing RA (they were positive for anti-CCP antibodies and had signs of inflammation on MRI). Half were given abatacept and half got a placebo for six months, then the patients were followed for a year.

They found that about 60 percent of people in the treatment group showed signs of improvement on MRI inflammation compared to about 30 percent of people in the placebo group. Arthritis developed in 17 people on placebo but only in four on abatacept.

The results suggest that intervening early could delay or prevent the onset of RA in those at high risk for it.

“Why do we wait until someone has really fully established rheumatoid arthritis before we start treating?” rheumatologist Arthur Kavanaugh, MD, said about the research in a video on RheumNow. “We don’t do that with cardiovascular disease. We don’t wait until someone has their first MI [heart attack] to start lowering their cholesterol.” The challenge, he acknowledges, is that the earlier in the course of disease someone is, the harder it is to know if it truly is preclinical RA, which could lead to a risk of over-treating.

2. ‘Fibromyalgianess’ with rheumatoid arthritis is linked with using long-term steroids

Research shows over one-third of people with RA show “fibromyalgianess” — a cluster of symptoms associated with greater sensitivity to pain. While disease-modifying drugs can treat some RA pain, they’re not as helpful for pain that is unrelated to disease activity. This may spur people with fibromyalgia-related pain to use other medication to treat their lingering pain.

A team of researchers, led by Beth Wallace, MD, of the University of Michigan, studied how fibromyalgianess might affect the use of glucocorticoid medication in about 100 RA patients who were on prednisone when the study began. They found that 57 percent of people with low fibromyalgia symptoms were still on steroids three months later, compared to 84 percent of those with high or very high fibromyalgia symptoms.

Because they also looked at participants’ swollen joints and levels of C-reactive protein, researchers could take into account disease activity. They found that “high fibromyalgianess” is associated with persistent steroid use, independent of inflammatory activity. The findings suggest that non-inflammatory pain from fibromyalgia may be misclassified as being related to inflammation, causing patients to take long-term steroids perhaps unnecessarily.

3. Low-dose rituximab may work well people with rheumatoid arthritis in low disease activity

Rituximab is a biologic medication typically used for people with hard-to-treat rheumatoid arthritis, typically given every six months. According to Dutch research presented at ACR, people who are in low disease activity on rituximab can remain there on a much lower dose of medication. They randomized 118 patients to receive 1,000 mg, 500 mg, or a very low 200 mg dose and followed them for about three years. Disease activity scores were comparable among the groups and so were other signs that the treatment was working well: The use of steroid medication was low and treatment persistence was high. (Only seven people switched treatment over the course of the study.)

The lead author Nathan den Broeder, MSc, said the study results have changed how his rheumatology clinic is treating rituximab patients, Healio Rheumatology reported. They start patients on a 1,000 mg dose and if they do well, taper them to 500 mg for six months, then further taper them to 200 mg if they continue to do well. “With this, we hope that patients have less side effects, and we hope to reduce the cost of treatment. Also, what we instantly gain is that the infusion time for patients is also reduced.”

Rituximab, of course, has gained a lot of notoriety this year for being linked with worse COVID-19 outcomes and poor response to the COVID-19 vaccine.

More research is needed to see whether reducing the dose of rituximab could have a positive impact there. Lower doses could possiblylead to less depletion of B cells or faster regeneration of B cells. B cells are parts of the immune system that can play a role in RA inflammation, but they’re also necessary for producing antibodies (such as against COVID-19).

4. The heart disease prevention benefits of taking statins outweighs the diabetes risk for people with RA

Underlying inflammation in rheumatoid arthritis increases the risk of heart disease, which in turn may also play a role in susceptibility to type 2 diabetes. Statins, which lower cholesterol and have anti-inflammatory properties, are staples of heart disease prevention treatment, but they can also slightly raise the risk of type 2 diabetes by raising blood sugar levels. So it’s important to understand these tradeoffs when deciding to start a statin: Do the benefits of someone with RA taking it to reduce their risk of heart disease outweigh the risk of developing diabetes?

Research led by Gulsen Ozen, MD, from the University of Nebraska explored this question by looking at data on 1,768 RA patients who started statins and comparing them with 3,528 similar patients who did not start statins. They did a separate analysis for the development of diabetes on 3,608 RA patients who started statins and 7,208 RA patients who did not.

They found that statin use was associated with a 32 percent reduced rate of cardiovascular disease, a 33 percent increase in the rate of type 2 diabetes, and a 54 percent reduced rate of overall death. The researchers concluded that the important reductions in heart disease and death outweighed the modest increase in type 2 diabetes risk.

“We know that RA patients are at higher risk for the development of CVD and death and type 2 diabetes compared to the general population. Moreover, RA patients are less frequently treated with statins than the general population, which is also concerning,” Dr. Ozen said in a press release. “We found that statins reduce both CVD and all-cause mortality, which were similar in magnitude. This may suggest that statins may have other beneficial effects in RA patients beyond lipid reduction. As rheumatologists, besides optimal disease activity control, we need to work on addressing the traditional CVD risk factors in our patients in conjunction with their primary care providers. We believe that our findings emphasize the benefits of statins in patients with RA.”

5. RA disease activity and function affect outcomes in people with RA-associated interstitial lung disease

Interstitial lung disease is a serious RA comorbidity with poor outcomes for patients. It tends to affect older patients who have been living with the disease a long time and doesn’t have many good treatment options. Thus, preventing ILD in the first place and figuring out how to help patients when they’re first diagnosed is very important.

A team of researchers looked at a group of 227 RA patients with ILD from a registry of U.S. veterans. The population was older (average age 69) predominantly male (93 percent), with a smoking history (85 percent). They found that RA disease activity and functional status were independent predictors of death: Higher disease activity scores or worse functional status scores were associated with a higher risk of dying over the study period, regardless of someone’s lung function score. However, having high disease activity and poor lung function was unsurprisingly the worst combination, with a 4.5-fold higher risk of death compared to those with normal lung function and low disease activity.

The researchers say these results demonstrate the need to make sure that optimal treatment for ILD includes controlling RA disease activity while addressing the lung disease manifestations.

Irish rheumatologist Richard Conway, MB, PhD, agreed with this takeaway on a RheumNow panel, saying that “when we have patients with rheumatoid arthritis interstitial lung disease, the first thing you need to do is control the rheumatoid disease.”

6. Who is likely to get nausea or hair loss while taking methotrexate for RA?

As a first-line treatment for rheumatoid arthritis, methotrexate is a widely prescribed disease-modifying drug that is well-studied and has been used for decades to treat other conditions. But many patients struggle with side effects like nausea and fatigue and worry about potential hair loss. It would help to know if certain characteristics were associated with an increased risk for experiencing such side effects, and UK researchers set out to do just that in new research on 1,069 patients with RA who were surveyed when they first started taking methotrexate and then followed for a year.

Researchers found that one-third (31 percent) of people reported nausea and 8 percent of people reported hair loss. Women were more than twice as likely as men to report nausea and almost four times more likely to report hair loss. Older age was associated with less nausea. Consuming alcohol while using methotrexate was associated with more nausea and hair loss. Higher disease activity at the start of the study was associated with increased odds of nausea too.

Researchers plan to continue studying whether other factors may be associated with reducing methotrexate side effects, such as folic acid supplements or taking an injectable form rather than oral pills.

Research like this is helpful because it validates patients’ experiences and can make you more informed when you talk to your doctor about your concerns when starting a medication.

7. There’s more proof that using steroids for RA is linked with serious heart disease risks

While steroids have always carried a long list of side effects, more research is emerging on just how risky they can be when it comes to serious heart events — even when they’re used for relatively short periods of time or in low doses. One study from researchers from the University of Pennsylvania and the University of Alabama found that for older adults (Medicare patients) on stable disease-modifying (DMARD) therapy, long-term use of low-dose corticosteroids was linked with an increased risk for heart attack or stroke, and the risk increased with steroid dose size.

A separate study looked at data on 26,239 U.S. veterans with RA, taking into account their cardiovascular risk factors, whether they were prescribed glucocorticoids, and for how long. Researchers found that just 30 days of using glucocorticoids was associated with a 14 percent increased risk of having a major cardiac event over the next six months — independent of their baseline risk factors for heart disease, previous steroid use, or other indicators of RA disease activity, such as biologic use.

Despite reducing inflammation, steroids increase the risk for cardiovascular-related events because they can increase blood pressure and blood sugar, among other things. While the oft-recommended advice is for people to take the lowest doses of steroids for the shortest time possible, it’s important to acknowledge that 1) this can still come with risks, and 2) this isn’t always possible for patients who rely on steroids to help them cope with flares or who’ve become accustomed to taking them as part of their treatment strategy.

8. Active rheumatoid arthritis is linked with an increased risk of dementia over time

Mayo Clinic researchers set out to study which factors may be associated with an increased risk of dementia in people with rheumatoid arthritis over time, following a cohort of people who were diagnosed with RA between 1980 and 2014. (People were followed until they died, moved, or until the study was concluded at the end of 2019.) Out of 1,366 patients in the study, 107 developed dementia (8 percent).

Though age itself was a risk factor, the researchers also found that joint swelling — a sign of clinically active arthritis — was linked with an elevated risk of developing dementia. So were a number of comorbidities: diabetes, heart disease and stroke, and heart failure.

Research like this further emphasizes how important it is to treat inflammation in RA not just to protect against permanent joint damage and disability, but also because it plays a role in serious long-term chronic diseases.

9. Experts are learning more about immune system proteins and antibodies associated with cardiovascular disease in RA

It’s widely known that inflammation in RA is linked with an increased risk of heart disease, but how can we get more precision about which RA patients might be at increased risk beyond looking at measures of traditional risk factors like cholesterol and blood pressure, which most certainly don’t tell the whole story?

Two studies from research teams led by Tate Johnson, MD, of the University of Nebraska Medical Center, provide some interesting clues. In one, the researchers studied a group of 2,712 U.S. veterans with RA over time, looking to see whether there was a link between blood levels of inflammatory proteins and their risk for a serious cardiovascular event like a heart attack or stroke.

They found several that were associated with the risk of heart events, even after the researchers accounted for traditional risk factors and RA disease activity. Even people who were in low disease activity or remission at the start of the study who had higher levels of these chemicals were at an increased risk.

In the other study, the research team looked at U.S. veterans with RA for the presence of autoantibodies, and found that higher concentrations of several different autoantibodies were linked with a serious heart-related event or death, which they say supports the hypothesis that autoantibodies may directly contribute to excess heart disease risk in RA.

The future of cardiovascular disease prevention in RA could involve screening patients for the presence of inflammatory proteins and autoantibodies in order to identify high-risk patients and intervene sooner.

10. Heart disease risk is high in many people with rheumatoid arthritis even right after diagnosis

When you were first diagnosed with RA, did you and your rheumatologist or primary care doctor talk about its impact on your heart health? Dutch research at ACR shows this may be a very important conversation to have. The researchers screened every newly diagnosed RA patient for heart disease risk, using a standard heart disease risk calculator (and applying a 1.5 multiplier to account for RA as a factor, which is a crude way to account for the increased risk that RA confers).

Out of 53 people screened so far in the study, 43 percent of new patients had an intermediate or high 10-year heart disease morbidity risk and 76 percent had an intermediate or high 10-year mortality risk. Importantly, many of the patients had underdiagnosed and undertreated heart disease risk factors, such as high cholesterol and high blood pressure — which are very treatable with lifestyle changes and medication.

If you haven’t talked to a provider about your heart health lately (or ever), now’s the time.

11. The reasons RA patients don’t change therapies stay remarkably steady over time

Changing RA medication is not a decision many people make lightly — there are many concerns and fears to consider, from worries about new side effects to whether the new drug will work better or worse than the old one. But as more RA medication options become available, patients will have to contend with such choices and so it’s important for doctors and patients to be aware of the factors that go into this thinking so they can work together as a team to figure out what’s right for a given person in a given situation.

A study at ACR investigated patients’ reasons for being unwilling to change medications by repeating the questionnaire from a pivotal study that was conducted 15 years earlier. The original study from 2006 had more than 6,000 respondents and the 2021 study had more than 1,600 respondents — but interestingly, there were 442 people who took the survey both years, so researchers could compare their answers. They found that while overall, fewer people were unwilling to change therapy in 2021 than in 2016, the reasons remained consistent. They included: satisfactory control over RA, risk of side effects, fearing loss of disease control, the doctor thinking their current treatment was best, and lower levels of pain. Costs and insurance company hassles were less of a barrier to switching in 2021 than in 2006.

What’s particularly important about research like this is that it helps providers better understand where patients are coming from. Each patient may have a unique mix of concerns and/or needs to address before they are comfortable starting or changing a medication.

You Can Participate in Rheumatoid Arthritis Research Too

If you are diagnosed with rheumatoid arthritis or another musculoskeletal condition, we encourage you to participate in future studies by joining CreakyJoints’ patient research registry, ArthritisPower. ArthritisPower is the first-ever patient-led, patient-centered research registry for joint, bone, and inflammatory skin conditions. Learn more and sign up here.