The COVID-19 pandemic may have changed the format of this year’s annual medical meeting of the American College of Rheumatology — it was held completely virtually — but it did not disrupt the sharing of important research that directly impacts people living with rheumatoid arthritis (RA).
The CreakyJoints team combed through hundreds of studies, attended sessions from top rheumatoid arthritis experts, and asked our team of patient and physician advisors to share the updates they deemed most important.
We curated this guide to rheumatoid arthritis research and trends from ACR that you should be aware of.
For more research breakthroughs from ACR Convergence 2020, check out our main guide: ACR 2020: 100+ Arthritis and Rheumatic Disease Updates Patients Must Know About.
1. New RA treatment guidelines call for reducing the use of steroids and ‘triple therapy’
At ACR meetings, it is common for new disease treatment guidelines to be shared with attendees. These guidelines are updated every few years through a robust process that involves evaluating the latest scientific research to determine best practices for treating a condition — in this case, rheumatoid arthritis — based on the quality of available evidence.
More recently, ACR’s guideline development process has included the input of patients as well as clinicians and researchers. The Global Healthy Living Foundation’s own Shilpa Venkatachalam, PhD, Associate Director of Patient-Centered Research, participated in the panel. She lives with rheumatoid arthritis herself.
“Patients with RA were involved at every step of the process and these recommendations truly reflect their perspectives. By including their personal experiences with different therapies, including their effectiveness, ease of use and side effects, the recommendations reflect the ACR’s goal of shared decision making between the rheumatologist and patient,” says the RA guidelines’ Principal Investigator Liana Fraenkel, MD, MPH, Professor Adjunct in the Division of Rheumatology, Allergy and Immunology at Yale University School of Medicine.
The guidelines, which focus strictly on medications for treating rheumatoid arthritis, are still under peer review and should be officially published soon. Future guidelines will cover non-drug therapies (such as lifestyle changes) and vaccines. Doctors use such guidelines to help make evidence-based decisions about what treatments to recommended.
An update to the 2015 rheumatoid arthritis treatment guidelines, this version contains 44 recommendations, seven of which are “strong” — which means there is lots of evidence for them — and 37 are “conditional.” This means there’s less certainty about the benefits and risks. Highlights include:
- Minimizing the use of glucocorticoids (such as prednisone) due to serious side effects associated with these drugs
- Starting patients on methotrexate and continuing with this treatment instead of rapidly switching to another disease-modifying anti-rheumatic drug (DMARD)
- Using a biologic or targeted synthetic DMARD (like a JAK inhibitor) instead of triple therapy (when patients take methotrexate, hydroxychloroquine, and sulfasalazine at the same time)
- Continuing medications is conditionally recommended over tapering; tapering should only be considered in people who have met their target for treatment for more than six months
It’s important to remember that guidelines are guidance for doctors, not hard-and-fast rules. RA is a complex disease that may affect patients in different ways, so rheumatologists often need to individualize management approaches and decision making.
We will be sharing more details about the treatment guidelines when they are published.
2. The benefits of the JAK inhibitor upadacitinib (Rinvoq) last beyond a year of treatment
Upadactinib (Rinvoq) was FDA-approved for rheumatoid arthritis last year. A JAK inhibitor, it’s an oral pill that works on targeted immune system pathways to reduce inflammation.
After a medication is approved, researchers continue to study how it performs over time. Previous research had shown that upadacitinib outperformed methotrexate up in patients who were randomized to take one or the other for 24 weeks (six months). Now, in study data presented at ACR, upadacitinib was compared to methotrexate for a longer period of time: 48 weeks and 72 weeks.
The results showed that more patients achieved at least a 20 percent improvement in their disease activity (a measure called the ACR20) on upadactinib (Rinvoq) compared to methotrexate at both 48 weeks and 72 weeks. For example, about 70 percent of people on upadactinib achieved an ACR20 response compared to 50 percent of people taking methotrexate. More patients on upadactinib also achieved what’s known as an ACR50 response (50 percent improvement) than those on methotrexate.
As more therapies for rheumatoid arthritis become available, it gives doctors more options to decide which medication is right for a given patient—and when.
There is even some debate as to whether medications such as JAK inhibitors could even be given to RA patients as a first-line treatment before methotrexate, though this is not currently recommended.
3. If you don’t do well on one JAK inhibitor, should you try another?
This is an important question as more types of JAKs continue to be approved for rheumatoid arthritis. There are currently three FDA-approved in the U.S.: tofacitinib (Xeljanz), baricitinib (Olumiant), and upadacitinib (Rinvoq). Spanish researchers shared results from a small observational study of 31 RA patients who started one JAK and then switched to another. Most (87 percent) had already taken biologic medication prior to taking a JAK. Half of the patients received tofacitinib first, and the other half got baricitinib first. Patients stayed on the first drug for five months on average; most stopped taking it because of inefficacy or side effects.
The researchers found that most patients stayed on the second JAK medication (only 9 stopped taking it, and all said it was because of inefficacy) and conclude that their data suggested that “failure to the first does not reduce the chance of response to the second.”
Switching patients from one biologic to another in the same category — for example, drugs that target TNF, such as adalimumab (Humira) and etanercept (Enbrel) — is already commonplace in RA treatment.
“These molecules [JAKs] are similar [to each other], but they’re different,” rheumatologist Arthur Kavanaugh, MD, Director of the Center for Innovative Therapy in the Division of Rheumatology, Allergy, and Immunology at the University of California at San Diego said in a RheumNow video. It’s important for rheumatologists to know that you can perhaps switch from one to another and have good outcomes and improve disease activity on the second, he added.
4. There is more promising research on vagus nerve stimulation for hard-to-treat rheumatoid arthritis
The vagus nerve runs from the brain, through the face and neck, and down into the abdomen. In addition to other functions, it is also the home of the inflammatory reflex, a pathway that appears to be crucial for detecting and modulating inflammation. Previous preliminary studies have shown that implanting a small device (about the size of a nickel) in the neck to stimulate the vagus nerve could tamp down inflammation in people with rheumatoid arthritis, particularly who were not responding well to inflammation-lowering medications.
At ACR, researchers presented a pilot study that tested a wearable device to stimulate the vagus nerve (which is less invasive than having a surgical procedure). It included data on 27 patients with active rheumatoid arthritis who did not respond to conventional disease-modifying medications (such as methotrexate). Many patients experienced improvements in disease activity and physical function and researchers said the device was well tolerated.
Larger studies that include control groups are needed to “confirm whether this non-invasive vagus nerve stimulator might offer an alternative approach to the treatment of RA,” researchers said.
There was a lot of important research about the burdens and impacts of comorbidities at ACR this year.
“We knew many rheumatic and musculoskeletal diseases are associated with other chronic conditions — called multimorbidity — but studies at the meeting are characterizing the unique patterns of multimorbidity and how multimorbidity impacts disease outcomes such as treatment and achieving treatment targets,” says rheumatologist Bryant England, MD, Assistant Professor of Internal Medicine at the University of Nebraska Medical Center in Omaha.
“Many of us need specialists to determine the comorbidities causing us pain and symptoms outside of our arthritis diagnosis,” says patient advocate Eileen Davidson, who lives with rheumatoid arthritis and reported on ACR for CreakyJoints. “For example, fibromyalgia, depression, neuropathy, osteoarthritis, or irreversible joint damage may be causing pain even though the original arthritis diagnosis is well controlled. Research at ACR showed that the these overlapping disease processes is common in RA. We need doctors to identify and help us manage all of these patterns of comorbidities in order to improve our health and outcomes.”
5. RA patients with a lot of comorbidities are less likely to achieve targets for low disease activity
Rheumatologists generally follow a strategy called “treat to target” in rheumatoid arthritis, which means identifying a target — such as low disease activity or remission — and adjusting treatment dosages and types until the goal can be met. But it’s not well understood whether people who have a lot of co-occurring conditions along with their RA — what doctors call multimorbidity — have the same outcomes as people without the burden of other health issues.
Researchers, led by Dr. England, studied data on a group of rheumatoid arthritis patients who were in high or moderate disease activity (meaning, they had not yet hit their “target”) and looked at whether they started any new medications and had follow-up visits, along with the extent of their comorbidities.
They found that patients with a lot of comorbidities were as likely as those without them to start new therapies, but they were much less likely to achieve low disease activity or remission. In fact, people with the “highest burden of multimorbidity” had approximately half the odds of achieving target RA disease activity compared to people with the lowest burden of multimorbidity.The researchers concluded that “broader management efforts targeted at multimorbidity may be needed to optimize RA disease control in these patients.”
6. Advanced therapies for rheumatoid arthritis are linked with decreased dementia
Inflammation is thought to play a role in degenerative neurological diseases like Alzheimer’s —and previous research has shown that conditions like rheumatoid arthritis can increase the risk of dementia. But more research is needed on whether disease-modifying medications — which reduce inflammation — could also help reduce dementia. A team of researchers from Hospital for Special Surgery and the University of Alabama at Birmingham set out to study this, analyzing Medicare claims data.
After looking at data on 141,326 people with rheumatoid arthritis, which medications they took to treat it, and subsequent incidences of dementia over time, the researchers concluded that people who took biologics or targeted disease-modifying drugs (such as JAK inhibitors) had a 17 percent lower risk for dementia than people taking conventional disease-modifying drugs (drugs in this class include methotrexate, hydroxychloroquine, and sulfasalazine).
Dementia risk was comparable, however, between people on different kinds of biologics and targeted therapies, which suggests that “decreased risk is possibly explained by the overall decrease in inflammation rather than a specific mechanism of action,” the researchers concluded.
7. Fatty liver is common in people with rheumatoid arthritis
Non-alcoholic fatty liver disease is the most common liver disorder in Western countries. Many of the same risk factors for fatty liver (called hepatic steatosis) are common in people with rheumatoid arthritis, including obesity, high blood pressure, high cholesterol, insulin resistance, and high levels of inflammation.
A team of researchers from Columbia University in New York City studied the presence of fatty liver in rheumatoid arthritis patients, conducting abdominal CT scans in 235 people with rheumatoid arthritis and comparing the results to those of a very large group of control patients (6,615) who did not have RA.
They found that the presence of fat in the liver was more than double in RA patients compared with controls.
Because some common RA medications, such as methotrexate, can impact liver function, researchers then did further analysis on just the RA patients. However, they did not find differences in the fatty liver by medication type among people with RA. Among those with RA, people with fatty liver had higher levels of C-reactive protein (a measure of inflammation) and they were more frequently positive for the antibody rheumatoid factor than RA patients who did not have fatty liver.
“It does seem that it’s possible that RA could have metabolic consequences that could put patients at risk for liver damage,” said rheumatologist Jeffrey Sparks, MD, Associate Physician at Brigham and Women’s Hospital in Boston, in a video for Healio Rheumatology, noting that “these are labs we monitor all the time.”
8. The ‘lipid paradox’ could explain why some RA patients are at a surprisingly higher risk of heart disease
In the general population, having low LDL (“bad”) cholesterol means having a lower risk for cardiovascular disease. But in people with rheumatoid arthritis, low LDL cholesterol has been linked with unexpectedly high cardiovascular risk, a surprising phenomenon known as the “lipid paradox.”
Now, a study at ACR from UCLA researchers sheds more light on what may be causing this paradox. The researchers did heart CT scans of 150 rheumatoid arthritis patients without known cardiovascular disease, looking for plaque in the arteries as well as other signs of damage. They grouped patients into three groups based on their LDL cholesterol levels.
They found that people with the lowest levels of LDL had a higher burden of coronary plaque and 2.8 times greater likelihood of extensive or obstructive disease compared to people with LDL greater than 70 mg/dL.
What gives? It seems to be quality of LDL, not quantity, that matters here, noted Dr. Sparks in a Healio video. The cholesterol in the low LDL group was very oxidized, which means associated with more inflammation. RA patients with low LDL may have fats and proteins in the blood that are directly causing inflammation and damage in the coronary blood vessels.
It’s important for doctors and patients to be aware of this counterintuitive finding because “the lipid paradox could lead you in the wrong direction,” says Dr. Sparks. It could make you think your heart is healthy because of low LDL when it could be the opposite situation. “We need to better understand how to reverse this, because this is a big issue for our patients,” he said.
9. A new biomarker test can help predict the risk of cardiovascular disease in rheumatoid arthritis better than just assessing traditional risk factors
For years, rheumatologists have used a blood test called a multi-biomarker disease activity (MBDA) score (known as Vectra) to check for levels of inflammation beyond just a single measure, such as C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR). The test looks at a dozen different proteins and molecules in the blood, which can provide a more accurate picture of inflammation as well as the risk of progressive joint damage in the future.
Now, research shows that the same multi-biomarker disease activity (MBDA) score can be used to help predict heart disease risk in rheumatoid arthritis patients.
In one study, researchers looked at a large group of RA patients (44,379) that was younger than Medicare patients (who were studied in the initial development and validation of the test). The test combines the original Vectra biomarkers with three additional ones plus some traditional heart disease risk factors (whether a person has diabetes, high blood pressure, their smoking status, and their heart disease history). The study found that a patient’s Vectra-based heart disease risk score was a significant predictor of heart disease risk.
A different study (in a group of 10,275 Medicare patients with high rates of comorbidities like diabetes and high blood pressure), the Vectra score was shown to have good accuracy, especially in specific patient groups who are likely to be at higher cardiovascular risk and would especially benefit from such testing.
The cardiovascular version of the test will be available early next year. You and your rheumatologist can discuss whether it’s right for you.
10. Many studies demonstrate the burden of lung disease in rheumatoid arthritis
Interstitial lung disease (ILD) is a known complication in rheumatoid arthritis, and one that’s linked to serious outcomes, including death. It’s a group of disorders characterized by inflammation and scarring of the interstitium, which surrounds the air sacs.
One study from a team of French researchers sought to estimate the prevalence of lung disease in RA patients who have been living with RA for a while (13 years on average). In 175 patients who had lung scans, the prevalence of subclinical lung disease — meaning that patients had signs of damage but not a diagnosis of ILD — was 18 percent after 13 years of disease duration. “The occurrence of ILD is not a rare event,” researchers concluded.
Separately, doctors from the Mayo Clinic in Minnesota and Brigham and Women’s Hospital in Boston studied which lifestyle factors are associated with interstitial lung disease, comparing RA patients with lung disease (84) to RA patients without (243). The found a few that were significant: obesity, high levels of C-reactive protein (a measure of inflammation), poor functional status, and a strong history of smoking. But they noted that “the overall ability to predict RA-ILD based on lifestyle and clinical factors was modest.”
The authors suggested that more research is needed to see whether weight loss and quitting smoking can delay or prevent the onset of lung disease, while adding that other factors, like biomarkers, may be needed to better predict which RA patients are likelier to get lung disease than others.
Another study from Brigham and Women’s researchers suggests that rheumatoid arthritis has a negative impact on lung function that is separate from having ILD. Researchers looked lung function test results from a large group of UK patients, comparing those with RA to those without. They found that RA patients were much more likely than the general population to have abnormal lung function tests, completely irrespective of smoking and other confounding variables.
11. Sleep apnea is common (and undertreated) in rheumatoid arthritis
Researchers from the University of California, San Francisco recruited 63 people with rheumatoid arthritis and gave them a device to wear on the wrist at home overnight to detect sleep apnea. Based on the results, researchers categorized patients into three different groups: normal, mild, moderate, or severe obstructive sleep apnea. They found that 35 percent of people had mild sleep apnea, 38 percent had moderate sleep apnea, and 17 percent had severe sleep apnea.
But the researchers noted that “most sleep apnea was unrecognized and would not be identified with current screening measures. OSA is linked to multiple health problems, including cardiovascular disease and fatigue, both of which are common in RA.”
They suggested that doctors consider screening for sleep apnea and treat it as a risk factor for poor outcomes in RA.
Remission and Tapering
12. How common is *lasting* remission in early rheumatoid arthritis? Not very.
Research suggests that diagnosing rheumatoid arthritis and starting treatment as early as possible is key to increasing the chances of achieving remission. But less is known about how long remission lasts once achieved, or what factors contribute to whether remission lasts or not.
Canadian researchers reviewed data on people in the Canadian Early Arthritis Cohort (CATCH), a group of patients whose RA is diagnosed relatively early (they had symptoms for less than one year). They focused on patients who had active disease at the time they joined the cohort, then later achieved remission — and then followed them for 12 to 24 months after that.
What they found: 55 percent of people achieved remission in the first place. Over the follow-up period, 47 percent of patients sustained remission for 12 months and 40 percent sustained it for up to 24 months. It was more common for people to shift from remission to low disease activity than to moderate or high disease activity.
Factors associated with remission not lasting included having more comorbidities, being seropositive, smoking, and being female. The researchers call for more careful monitoring of patients who are at higher risk for “transient remission.”
13. If you achieve remission on methotrexate and a biologic, you may be better off tapering the MTX than the biologic
“Combination therapy” — in which a patient starts taking a conventional disease-modifying drug like methotrexate and then adds a biologic — is common in rheumatoid arthritis. But if someone is able to get to remission on this combination and then wants to attempt to taper their medications, which drug should they reduce or stop?
Researchers, led by University of Alabama at Birmingham rheumatologist Jeffrey Curtis, MD, looked at RA patients who were taking methotrexate and the biologic etanercept (Enbrel) who were considered to be in remission. After six months, patients who were still in remission (253) were randomized into three groups: methotrexate only, etanercept only, and a combination of both. After 48 weeks, just 29 percent of people in the methotrexate-only group stayed in remission, compared to about 50 percent of people in the etanercept-only group and 53 percent of people in the combination group.
“Similar proportions of patients maintained remission with etanercept monotherapy as compared to continuing with [combination therapy], so the implication is that probably if you are doing that well on both treatments, you can continue etanercept, stop methotrexate, and the majority of those people are going to do just as well,” Dr. Curtis said during an ACR presentation. Dr. Curtis is also Co-principal Investigator of ArthritisPower, our patient-centered research registry.
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.
Curtis JR, et al. External Validation of a Multi-biomarker-Based Cardiovascular Disease Risk Prediction Score for Rheumatoid Arthritis Patients [abstract]. Arthritis & Rheumatology. November 2020.https://acrabstracts.org/abstract/external-validation-of-a-multi-biomarker-based-cardiovascular-disease-risk-prediction-score-for-rheumatoid-arthritis-patients.
Curtis JR, et al. Maintenance of Remission After Withdrawal of Etanercept or Methotrexate in Patients with Rheumatoid Arthritis in Sustained Remission on Combination Therapy: Results from a Randomized, Double-blind, Controlled Trial [abstract]. Arthritis & Rheumatology. November 2020. https://acrabstracts.org/abstract/maintenance-of-remission-after-withdrawal-of-etanercept-or-methotrexate-in-patients-with-rheumatoid-arthritis-in-sustained-remission-on-combination-therapy-results-from-a-randomized-double-blind-co.
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Interview with Bryant England, MD, Assistant Professor of Internal Medicine at the University of Nebraska Medical Center in Omaha
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Rheumatology Round-Up with Drs. Kavanugh & Cush. RheumNow. November 10, 2020. https://rheumnow.com/news/rheumatology-round-drs-kavanaugh-cush.
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Video: RA and the ‘lipid paradox’ need awareness, understanding. Healio Rheumatology. November 13, 2020. https://www.healio.com/news/rheumatology/20201111/video-ra-and-the-lipid-paradox-need-awareness-understanding.
Video: Risk for Liver Damage May Be Associated with RA. Healio Rheumatology. November 11, 2020. https://www.healio.com/news/rheumatology/20201111/video-risk-for-liver-damage-may-be-associated-with-ra.
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