This year’s American College of Rheumatology’s annual scientific meeting, which took place November 1 to 10, included more than 2,000 abstracts and expert presentations from over 320 clinicians, researchers, and health experts. More than 14,000 rheumatology professionals and patients from 110+ countries attended the virtual conference online.

Here are some key RA research updates:

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Rituximab increased odds of COVID-19 hospitalization vs. DMARDs for RA patients

Patient use of rituximab compared with conventional synthetic disease-modifying antirheumatic drugs was associated with worse COVID-19 outcomes in patients with rheumatoid arthritis (RA), according to a presenter at ACR Convergence 2021.

“The COVID-19 pandemic led to several questions regarding the safety of DMARDs that patients with rheumatic diseases use for their management,” said Namrata Singh, MD, MSCIFACP, assistant professor at the University of Washington.

Among different DMARDs, rituximab (Rituxan, Genentech) has a unique mechanism of action with depletion of B cells that can last for several months. Dr. Singh and his research team considered this in their study with the aim to shed light on the comparative safety of rituximab compared with other DMARDs in patients with RA.

“Interestingly, in our study, we did not find an association between rituximab use and mortality from COVID-19,” explained Singh. “This contrasts with a few other studies that did observe an association. We speculate that this could be because prior studies did not adequately adjust for COVID-19 treatments, especially those used during COVID-19 hospitalization, as we did in our analyses.”

No DMARD use was also found to be associated with significantly higher odds of hospitalization in patients diagnosed with COVID-19, according to the study.

“Findings from our study can guide patients, providers and policymakers regarding the increased risks associated with rituximab use during the COVID-19 pandemic,” the researchers said in the presentation.

The data also highlight the need for continued close monitoring of patients on rituximab, the need for COVID-19 vaccination and boosters, and continuation of the other preventive measures, including masking, social distancing and avoiding unnecessary travel.

Black and Hispanic RA patients have higher disease activity than white patients

New research presented at the ACR annual meeting found that racial and ethnic disparities for disease activity persist in people with RA. Black and Hispanic RA patients often had higher disease activity and lower self-reported functional status (basic activities of daily living, e.g., feeding, bathing, dressing personal hygiene and walking) when compared with white patients.

Research has shown that there are differences in disease activity and clinical outcomes for people with RA across different racial and ethnic groups in the United States. These disparities exist across the healthcare system, and these inequities impact both patient experience as well as patient clinical outcomes. However, this has not been studied as extensively in RA as in other disease areas, so there is still a need to understand the magnitude of health disparities in RA. The authors conducted this new study to learn more about these disparities and how they may have changed over time.

According to the presenter of the study, Jacqueline O’Brien, ScD, a clinical epidemiologist:
“The study tells us that, in a population of people who have access to a clinic, have access to treatment, that we’re seeing a lot of differences between the racial and ethnic groups. I think the findings can serve as a reminder to clinicians that it’s important to be mindful that patients are coming from diverse racial and ethnic backgrounds. They may have different needs to achieve similar levels of success with advanced therapy.”

There are many factors that contribute to health inequality, including access to care, socioeconomic status, systemic racism and other social determinants of health (non-medical factors that influence health outcomes).

Dr. O’Brien added. “Certainly, more research is needed to understand how these factors interact and result in different clinical outcomes for racial and ethnic groups. We need to identify where the disparities exist, so that we can better target therapy and improve care, for all patients.”

A key long-term goal is really recruiting diverse populations into future research. RA research has focused predominantly on white populations, and we need more information on the epidemiology of RA (determinants, distribution of diseases), the disease course, the patient reported outcomes in patients of different racial and ethnic backgrounds, and ultimately a complex multifactor solution is going to be needed to address health disparities in RA.”

Going deeper

The underrepresentation of Black, Indigenous People and People of Colour (BIPOC) patients in RA research is a very important finding in and of itself. It suggests that racial minorities are generally being excluded from networks in the arthritis patient community. This means the voices and experiences of BIPOC people living with RA are largely going unheard. This is a particularly significant problem because BIPOC people are more likely to experience negative health outcomes (due to systemic racism) in RA.

A May 2021 study published in Arthritis Care & Research examined 65 ACR and EULAR practice guidelines and recommendations and found a troubling lack of clarity regarding race information, an “urgent need” for standardized race reporting and research with insufficient racial diversity that was used to make race-based recommendations for Black patients.

Higher risk of breakthrough COVID-19 infection in RA, gout, vasculitis patients

Patients with rheumatoid arthritis, gout, vasculitis and those with multiple autoimmune of inflammatory arthritis diseases were at greatest risk for breakthrough COVID-19 infection, despite full or partial vaccination, compared to those without autoimmune disease.

“People with rheumatoid arthritis, gout, vasculitis and multiple autoimmune diseases were significantly more likely to have breakthrough infections compared to people without immunosuppressed conditions,” said Jasvinder A. Singh, MD, MPH, of the University of Alabama at Birmingham, in his presentation at ACR Convergence 2021.

Dr. Sing concluded: “This data, we believe, is important information to guide patients, providers and policymakers. Although more research is needed, these findings support the use of a third vaccination in immunosuppressed patients.”

Vitamin D, omega-3 supplements reduced risk for autoimmune disease, including RA

The use of vitamin D3 or omega-3 fatty acid supplements over a 5-year period may reduce the incidence* of autoimmune disease (including RA) in older adults by 25% to 30%, according to data presented at ACR Convergence 2021.

*(Incidence is a measure of disease that allows us to determine a person’s probability of being diagnosed with a disease during a given period of time. Therefore, incidence is the number of newly diagnosed cases of a disease.)

“In past studies, inflammatory bowel disease, multiple sclerosis and type 2 diabetes have been shown to be more prevalent at northern latitudes, where circulating vitamin D levels are lower,” Karen Costenbader, MD, MPH, director of the Lupus Program at Brigham and Women’s Hospital, told attendees at the ACR meeting. “Both vitamin D and high residential UV exposure were associated with a decreased risk for rheumatoid arthritis among women in the Nurses’ Health Study in our past work.”

However, to date, no prospective randomized trials have tested the effects of vitamin D or omega-3 fatty acid supplementation on the incidence of autoimmune diseases over time, Costenbader noted.

“The reduced incidence of RA is very important for rheumatology,” Costenbader said. “The more pronounced effect after 2 to 3 years of use with vitamin D makes sense biologically and supports long-term use. There is an ongoing extension study confirming incident cases in further follow-up. The clinical importance of these results is very high given that these are well-tolerated, non-toxic supplements, and that there are no other known effective therapies to reduce incidence for autoimmune diseases.”

Glucocorticoid use in RA patients increases cardiovascular risk

According to data presented at ACR Convergence 2021, 30 days of glucocorticoid use in 6 months for RA patients is associated with 15% increased odds of major adverse cardiac events (MACE) in the next 6 months. Glucocorticoids medications are man-made versions of glucocorticoids, which are steroids that occur naturally in your body, and are very effective at reducing inflammation and suppressing the immune system.

“Up to half of RA patients in the United States use long-term glucocorticoids, despite previous work suggesting they increase major cardiovascular events,” said Beth Wallace, MD, MS, of the University of Michigan Medicine and the U.S. Veterans Affairs Ann Arbor Healthcare System.
“Earlier research suggests long-term glucocorticoid use is common among RA patients with traditional MACE risk factors, like hyperlipidemia, diabetes, hypertension and smoking, but we know little about the incremental effect of ongoing glucocorticoid use on MACE risk in RA, particularly as traditionally predisposed comorbidities might confound its assessment.”

Dr. Wallace added: “For example, RA patients who take steroids may be more likely to develop diabetes or hypertension, which, if not adjusted for, could confound an association between glucocorticoid exposure and MACE.”

The study results saw that just 30 days of glucocorticoid use in a 6-month period, even if discontinuous, is associated with a 15% increase in odds of MACE over the following 6-month period. This association appears not to be related to a patient’s baseline MACE risk, or to biologic and methotrexate use.

The Annual European Congress of Rheumatology 2019, hosted by the European League Against Rheumatism (EULAR), featured more than 14,500 attendees from 120 countries coming together to hear the best in rheumatology research and clinical advances. The scientific programme included presentations carefully selected from 4,900 abstracts submitted.

This week, EULAR published it’s The EULAR 2019 Report providing the highlights of some of the best presentations, focusing on the clinical and therapeutic findings that are able to change the way rheumatologists and other health professionals practice medicine.

How does it relate to the work of the Global RA Network?

As part of the work of the Global RA Network, our members have defined key elements of a RA model of care that address the complex, life-long issues facing patients and include all points of contact across the health care system.

At EULAR 2019, numerous presentations were related to the Global RA Network’s RA models of care key elements during the patient’s disease journey:

  1. Global RA Network Model of Care element: Medical Management

 As defined by the Global RA Network, the management of RA is complex and requires consistent and frequent monitoring with an arthritis specialist to ensure the effectiveness of treatment and care.

 Here are some highlighted EULAR research presentations on “medical management” for RA patients:

 EULAR revises its RA management recommendations

 The most notable recommendations to RA management discussed at the EULAR conference include:

  • no change to designating methotrexate as the first disease-modifying medicine to prescribe, before any biologic medicine;
  • no adoption of imaging criteria to determine whether a patient is in remission; and
  • no preference is to be given to biologic DMARDS over target synthetic DMARDS

Read more about EULAR revisions to RA management recommendations here:

Understanding why some RA patients do or don’t respond to methotrexate. Some newly diagnosed RA patients respond well to the disease-modifying drug methotrexate and others do not. Preliminary EULAR research found that there were differences in how bacterial genes functioned in people who did and did not respond to methotrexate. More research is needed to validate this work and to see whether the model applies to other patient populations. But the research does provide “the first step toward predicting methotrexate response in new-onset RA patients,” according to EULAR Congress News. See the abstract of the oral presentation:

New JAK inhibitor gets closer to RA approval. JAK inhibitors are targeted oral medications that can treat inflammatory autoimmune diseases.  Phase III clinical trial results for a new JAK – filgotinib – were presented at EULAR. The data showed that filgotinib helped prevent radiographic progression and improved physical function among RA patients who didn’t respond to methotrexate. More patients who took filgotinib achieved an improvement of at least 20 percent in American College of Rheumatology criteria (ACR20) after three months compared with patients on a placebo. “Its effectiveness and ease of use make it a potential monotherapy,” said investigator Bernard Combe, MD, PhD, from Montpellier University in France. He predicted that the drug could be on the market within two years. See the abstract of the oral presentation here:

It may be safe to taper prednisone in RA patients doing well on tociluzumab (Actemra). A new trial found that more than two-thirds of RA patients in remission or with low disease activity who tapered prednisone down to 0 mg/day over the course of six months while taking tociluzumab did not experience disease flares or experience adrenal issues (which can happen while weaning off steroid medication). “Tapering glucocorticoid treatment with an aim for complete discontinuation is worth considering for all patients once they achieve disease control in line with treat-to-target recommendations,” Gerd R. Burmester, MD, director of the department of rheumatology and clinical immunology at Charité-Universitätsmedizin Berlin and Humboldt University of Berline, said in the EULAR Congress News. See the abstract for the oral presentation:

It may be safe for RA patients doing well on tofacitinib (Xeljanz) to taper methotrexate. RA patients taking the JAK inhibitor tofacitinib (Xeljanz) plus methotrexate who achieved low disease activity may be able to stop taking MTX without worsening their disease activity. “These results may be used to inform treatment guidelines regarding optimal approaches for discontinuation of methotrexate in patients with rheumatoid arthritis,” study author Stanley Cohen, MD, of the University of Texas Southwestern Medical Center in Dallas, told MedPage Today.

Disease remission associated with 80% reduction in risk of cardiovascular outcomes in RA patients

RA patients who are in remission are 80 percent less likely than those with active RA to have a heart attack or stroke or develop congestive heart failure, according to new Italian research that analyzed data on nearly 900 patients. This is very encouraging news for patients who hear and worry about various RA complications because it indicates that controlling disease activity can reduce the impact of systemic inflammation on other organs. It also highlights the importance and the challenge of getting more RA patients into remission in the first place. Read more about the research:

Preventing gum disease may help manage RA symptoms. A large Japanese survey of rheumatoid arthritis patients found that those with periodontitis (inflammation of the gums) had significantly higher disease activity scores, worse physical function, and greater rates of infection than patients without gum disease. “Oral care is important for patients with rheumatoid arthritis because it appears to improve disease outcomes in clinical settings,” according to Ryoko Sakai, MD, of Tokyo Women’s Medical University, in EULAR Congress News.

  1. Global RA Network Model of Care Element: Shared Care

As defined by the Global RA Network, treatment decisions should be made through agreement between the patient and the healthcare team, and there must be adherence to the treatment regime.

image of healthcare team

Here are some research results presented at EULAR 2019 that focus on “shared care” for RA patients:

Patient-healthcare provider relationship key factor if patients take methotrexate as prescribed. Serbian researchers found that patients were more likely to be “non-adherent” to methotrexate if they reported needing better communication with their doctor about RA treatment. About one-third of patients in the study were considered non-adherent to MTX.  Patients have many questions about taking methotrexate. It may be the case that improving doctor-patient communication could alleviate some patient concerns. View the abstract here:

Doctors working with patients to manage their fatigue. In a session at EULAR titled “My Joints Hurt and I’m Overwhelmingly Tired: Fatigue in Rheumatoid Arthritis”, doctors reviewed how to recognize, assess, and treat fatigue in inflammatory arthritis patients.

“Fatigue remains a difficult-to-address patient concern,” says Maria Danila, MD, a rheumatologist at the University of Alabama Birmingham, who attended the session. Fatigue affects 40 to 80 percent of patients with rheumatic and musculoskeletal diseases, so it was encouraging to see clinicians making this topic front and center at EULAR 2019. See the speaker abstract:

Doctors helping patients are making exercise a key part of the treatment plan. In a session at EULAR called “Exercise: More Than a Wonder Drug”, attendees discussed “how to help and motivate patients to make [exercise] a habit so they can reap its long-term rewards.” Rheumatologists were advised that although their time with patients is limited and focused on assessing disease activity and reviewing medication management, they should also find the time to encourage physical activity with their patients. See the speaker abstract: 

  1. Global RA Network Model of Care Element: Patient Self Care

As defined by the Global RA Network, the RA patient should be fully educated about their medical conditions and the importance of closely following the treatment regime.

Here are some EULAR research highlights on RA patient self-care:

Obesity and smoking could be leading factors in RA patients not achieving remission in the first year of treatment. Canadian researchers sought to understand which factors contributed to RA patients receiving guideline-based care not achieving remission in the first 12 months of treatment after being diagnosed. They found that obesity in women and current smoking in men “were the strongest predictors of not achieving remission in the first 12 months” followed by non-use of methotrexate, higher baseline inflammation and longer symptom duration. Researchers suggested that lifestyle interventions such as “smoking cessation in men and weight reduction in women, and optimising methotrexate use may facilitate rapid reduction of inflammation, an essential goal of treatment in early RA.” Read the abstract:

Mediterranean diet may help RA patients, but more research is needed. There’s scant evidence to support specific diet recommendations to prevent or manage inflammatory arthritis, but many nutrition experts advise patients to follow a Mediterranean-style diet because of other data that links this style of eating to lower risks of heart disease, type 2 diabetes, and certain cancers. One French study from EULAR found that following a Mediterranean diet helped lower the risk of developing rheumatoid arthritis in women who used to smoke. An Italian study found that among people already diagnosed with RA, there was a correlation between following a Mediterranean diet and lower disease activity, although it was not statistically significant. Adhering to the Mediterranean diet was linked with lower rates of high blood pressure and better general health. Read the abstract:

Fatigue and rheumatoid arthritis

Fatigue is a common, persistent problem for rheumatoid arthritis (RA) patients. Affecting 40% – 80% of RA patients, fatigue is considered one of the most important disease outcomes by patients. Work disability is among the most important consequences of RA-related fatigue. According to Professor Jose Antonio da Silva, patients have identified fatigue as the principal barrier to employment and productivity. In a special EULAR session, Professor da Silva noted that numerous studies have demonstrated that fatigue in RA contributes to a higher likelihood of absenteeism at work, a higher prevalence of the various dimensions of work disability, and more consultations with physicians and referrals to therapists. A challenge for rheumatologists is determining how to measure fatigue in RA where there is no consensus on the most effective method of measurement and lack of a standardized assessment tool. Professor da Silva added that overall, the measurement of fatigue in RA entails several challenges because of its subjective nature.

To learn more about arthritis in the Canadian workforce and an upcoming program to support employees with arthritis, read this issue of JointHealth™ insight.

Delays in referral of new RA Patients

One of the key findings of the Global RA Network’s international survey on patient-reported experiences of RA models of care focused on a patient’s access to a specialist.

Our survey results revealed that 51% had to wait longer than three months for their first rheumatologist appointment and 33% of patients did not see their rheumatologist as frequently as recommended by guidelines.

In a study from the UK published in March 2019, researchers found similar delays for a RA patient referral to a first consultation.

Key findings included:
• The median time between symptom onset and rheumatology consult was 27.2 weeks (IQR 14.1-66 weeks).
• Only 20% of patients were seen within the first 3 months of symptom onset.

Researchers found multiple reasons for patients’ delayed referral to their first consultation with their rheumatologist:
• Delays were found along the patient journey; delays in primary care were particularly long.
• Delays were prolonged in patients who purchased over-the-counter medications or used ice/heat packs and took longer to seek help than those who did not.
• Patients with intermittent symptoms that developed slowly over time delayed longer for their first consultation compared to patients with persistent symptoms or symptoms that came on rapidly.

The study concludes that patient education and delays by primary care providers will require interventions to promote more timely referrals to rheumatologists.

Our most vulnerable RA patients

image of hay rolls on a farmIn our meetings and in our international survey, our Global RA Network has observed and discussed the RA models of care challenges faced by our underserved or vulnerable patient populations such as RA patients of lower income, with disabilities including mental illnesses, or from ethnic minority communities, rural communities and indigenous communities.

A recent study in Canada has found the risk for RA is twice as high among indigenous First Nations Canadian populations.

The study compared the prevalence and incidence of RA in a Canadian province, Manitoba, with the non-Native population and the indigenous First Nations population (who make up approximately 20% of the province’s population). First Nations populations carried a higher prevalence rate than non-First Nations populations. A particularly high increase in prevalence was reported in First Nations populations aged 29 to 48 years compared with non-First Nations populations in that age range.

Commenting on the study, Carol Hitchon MD, MSc, associate professor of medicine at the University of Manitoba said: “This increased prevalence and incidence was particularly striking for young women of childbearing age.”

The researchers also noted that although individuals in the First Nations group were more likely to visit a physician, they were less likely to visit a rheumatologist.

Several factors may contribute to the observed high prevalence and incidence of RA in First Nations,” Hitchon said. “We have shown previously that the general First Nations population in our region has high rates of a genetic condition (HLA-DRB1 shared epitope alleles) and also has high rates of exposure to environmental factors associated with RA. We do not know if additional social and historical factors play a role.”

The study concluded the burden of RA is likely to increase for First Nations populations, along with the increased need for rheumatology services. The researchers stated strategies to identify and address the factors that contribute to the increased risk of RA in First Nations are needed. Researchers finally concluded RA models of methods must be improved.

The American College of Rheumatology’s annual meeting is one of the world’s leading events in global rheumatology education. With over 450 sessions, the meeting provides opportunities for researchers, clinicians and patients to meet and share information with each other and first-hand access to the latest rheumatology research and clinical applications.

At the ACR annual meeting in November 2018, Dr. Janet Pope summarized RA research highlights from the meeting. Dr. Pope is a Professor of Medicine and Head of the Division of Rheumatology at Western University in Canada, where she leads a diverse research program that has impacted rheumatology worldwide.

Watch Dr. Janet Pope discuss RA research highlights from the most recent ACR annual meeting:

Learn more about RA research highlights from the ACR 2018 meeting:

RA and the Flu

Did you know RA patients have greater than two times the risk of influenza and flu-related illness? In many countries, RA patients are regularly included in priority groups thought to benefit the most from flu vaccinations. Although the flu vaccination is recommended in RA, the patient’s antibody response and effectiveness of the standard- dose vaccine are low.

A study by Doctors at McGill University in Montreal, Canada, was designed to find out whether a high-dose flu vaccine would improve protection for RA patients compared to the standard-dose vaccine. The researchers found patient responses to the high-dose vaccination were consistently higher.

What it means for RA patients

For patients with seropositive RA, the high-dose flu vaccine substantially improves the immune response to the vaccination compared to the standard-dose vaccine. Since RA patients are at higher risk for catching the flu, they should be vaccinated each year.

Patients should learn about the available flu vaccinations and doses so that they can make the best decisions with their rheumatologists.

JAK inhibitors: next generation treatment for RA patients

Biologics that work by inhibiting the tumour necrosis factor (TNF) have been used for several years and are well-established as an advanced therapy for RA. Over the last six years, new advanced therapies – Janus kinase (JAK) inhibitors such as tofacitinib and baricitinib)– have gained approval in numerous countries for the treatment of RA. Small molecule JAK therapies represent the first oral advanced therapy to treat RA. Before the introduction of JAK therapies, only therapies given by infusion or injection were available to moderate to severe RA patients.

At the ACR annual meeting in 2018, research for new JAK inhibitors – filgotinib and upadacitinib – was presented that showed strong efficacy and safety data results; not just in RA, but now also in psoriatic arthritis. Another finding in research presented at the ACR about JAK inhibitors is how quickly they seem to work. According to data, most patients notice a significant improvement in pain, and quality of life by as early as the first week of treatment.

The scientific evidence and the increasing number of approved JAK inhibitors, along with other JAK therapies currently under development, potentially may lead to them being considered as first line therapy, along with anti-TNF inhibitors, for RA patients based on their efficacy, safety and oral use.

What it means for RA patients

As RA patients can anticipate and should prepare to have advanced therapy conversations with their specialists about JAK inhibitors as a treatment choice for their disease.

Do you want to learn more about having the advanced therapy conversation? Please click here to enrol in JointHealth Education – an online course for RA patients:

Transitioning patients to biosimilars

The latest data were reviewed at the annual meetings of both EULAR and ACR in 2018 and continues to show transitioning to biosimilars is safe and effective over the long-term, and have done so over the past five years.

A biologic biosimilar is a medicine highly similar to another biologic medication already marketed in a country. A biosimilar enters the market after an originator patent expires. Since the introduction of the first biosimilar in 2006 in Europe, the EU has approved more than 30 biosimilars to date. According to the European Medicines Agency (EMA), the evidence acquired over 10 years of clinical experience shows that biosimilars can be used as safely and effectively in all their approved indications as other biologic medications.

Research and real world evidence on transitioning

Transitioning has been safely and effectively implemented with thousands of patients with autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis, gastrointestinal and bowel diseases in many countries in Europe. More than 90 current, high quality research studies have demonstrated the safety and efficacy of biosimilar transition. Data from randomized trials and from registries in Norway, Denmark, Germany and Sweden, tracking patients’ “real world” experience, show nearly identical results.

Communicating with patients on biosimilar transitioning

Research presented at the ACR and EULAR annual meetings has shown the importance of patient education before, during, and after a transition to a biosimilar.

During the first conversations about transitioning to a biosimilar, the way in which rheumatologists and other healthcare providers communicate with patients is key to ensuring a patient’s positive expectations about the transition. Rheumatologists, nurses and pharmacists must be able to clearly explain the safety, quality and benefits of biosimilars when answering patient questions about transitioning and help give them confidence to ensure smooth transition between biologic originators and biosimilars.

What it means for RA patients

Prior to transitioning, patients must be fully informed about the policy requiring the transition and have all available information about the biosimilar. Having this information can also ensure patients and rheumatologists have an informed and constructive conversation about why a patient’s treatment is being changed.

Want to learn more about biosimilars?

In 2018, the EMA published new, patient-focused materials that aim to make patients aware of biosimilars and how the EMA assures that they are as safe and effective as originators.

The new materials include an animated video, available in 8 European languages, that explains key features of biosimilars. Click here to view:

The video, available in eight European languages, explains that a biosimilar is not a generic, but that it is highly similar to an originator and has the same mechanism of action. The video also highlights the increased patient access that biosimilars have facilitated in the EU by making therapies more affordable for patients. It goes on to outline the EMA’s approach to regulating biosimilars and its post-marketing surveillance activities.

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