JointHealth™ express   June 8, 2021

Key research highlights from EULAR 2021

The EULAR Annual Scientific Meeting was held for the second consecutive year virtually where presentations were presented online featuring the latest research, clinical updates about the practice of rheumatology around the world. The meeting provided a combination of recorded and live presentations and discussions. This year’s program included more than 170 sessions held across 123 different virtual rooms over four days. Here are some of the key presentations from this year’s meeting.

Elderly patients not at increased risk of serious infections with biologic or targeted small molecule therapies compared to csDMARD

Elderly people with rheumatoid arthritis (RA) are generally at increased risk of serious infections. German researchers presented study findings* assessing the effects of newer classes of drugs such as biologic disease-modifying anti-rheumatic drugs (bDMARDs or biologics) and Janus kinase inhibitors (JAK) on the risk of serious infections in elderly people with RA (above 70 years of age).

Results of this study suggest that treatment with biologics or JAK therapies is not associated with an increased risk of serious infection in elderly patients compared to csDMARDs.** Researchers did find associations with an increased risk of serious infections for glucocorticoid use, higher disease activity, and having another underlying disease such as chronic pulmonary or kidney disease, or diabetes. The authors also found that being in better physical shape was associated with a decreased risk of having a serious infection.

*Strangfeld A, et al. Elderly patients are not at increased risk of serious infections when receiving bDMARDs or JAK inhibitors compared to csDMARD treatment. Presented at EULAR 2021; abstract OP0116.

**Conventional synthetic DMARDs include traditional medications such as methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, gold, salts and others.

Inflammation of the eye after medication is discontinued in children with JIA

Uveitis is an inflammation of the eye and is a common extra-articular manifestation associated with juvenile idiopathic arthritis (JIA). It can cause vision-threatening complications, and if left uncontrolled may even lead to blindness.

German researchers presented a study* at the 2021 EULAR annual meeting that analyzed risk of uveitis after discontinuing disease-modifying antirheumatic drugs (DMARD) in children with JIA.

This is the first prospective study** to look at the risk of uveitis after DMARD withdrawal. The findings show uveitis relapses are common. Patients who stop DMARD therapy are at high risk for uveitis within the first 3–24 months after discontinuation. Researchers recommended that rheumatologists and ophthalmologists should be aware about this risk, which should lead to regular uveitis screening after DMARD withdrawal.

*Klotsche J, et al. Risk for uveitis events after withdrawal of disease modifying antirheumatic drugs in the treatment of patients with extended oligoarthritis or rheumatoid factor negative polyarthritis. Presented at EULAR 2021; abstract OP0165.

**A prospective study watches for outcomes, such as the development of a disease, during the study period and relates this to other factors such as suspected risk.

Passive smoking and air pollution – links to arthritis development and poor response to therapy

There is increasing evidence that environmental air pollution is associated with people developing inflammatory arthritis. At the 2021 EULAR annual meeting, a large population-based study of French women reports passive exposure to smoking during childhood or adulthood increases the risk of developing rheumatoid arthritis (RA). A second study in Italy found that air pollution also has an impact – with air pollution levels showing an association with failure of biologic therapy.

In the study looking at the relationship between passive smoking and the risk of developing RA, passive smoking in childhood was positively associated with the risk of RA in the whole population.* Researchers then analysed each person’s own smoking status and found passive smoking in childhood was associated with RA among women who had never smoked themselves, but not among those who had ever smoked themselves.

When the authors looked at passive smoking in adulthood, there was also a positive risk association in the whole population. But when analysed again by individual smoking status, the association with increased RA risk was only among never-smoking women, not those who had ever themselves been a smoker.

These results suggest that smoking by-products – whether actively or passively inhaled – could generate autoimmunity, at least towards antigens** involved in the development of a person’s RA disease.

In another presentation, examining another link between the lungs and inflammatory arthritis, researchers looked at the association between concentration of air pollutants and response to biologic drug treatment in people with chronic inflammatory arthritis living in the Verona area of Italy.***

Air pollutants concentrations were higher before a switch or swap due to drug inefficacy. The authors concluded that environmental air pollution was a determinant of poor response to biologic treatment. Interventions to decrease fossil fuel combustion emissions might have beneficial effects on the persistence rate of biologic treatments in people with inflammatory arthritis.

*Nguyen Y, et al. Association between passive smoking in childhood and adulthood, and rheumatoid arthritis: results from the French E3N-EPIC cohort study. Presented at EULAR 2021; abstract OP0012.

**An antigen is any substance that causes your immune system to produce antibodies against it.

***Adami G, et al. Air pollution is a predictor of poor response to biological therapies in chronic inflammatory arthritides. Presented at EULAR 2021; poster POS0644.

Delay to diagnosis in axial spondyloarthritis

Axial spondyloarthritis (axSpA) is a type of inflammatory arthritis affecting the back. Research shows an average delay of around 7 years – and up to 15 years in some cases – during which time the condition can progress and lead to irreversible damage. Data indicates that women wait longer than men for a diagnosis, and there has been very limited progress in reducing the time to diagnosis. This delay has a hugely detrimental impact on a person’s quality of life. Because the disease frequently has early onset, individuals are left untreated – or with incorrectly treated symptoms – at a formative period in their life course.

At the 2021 EULAR congress, Dr Dale Webb and colleagues from the Axial Spondyloarthritis International Federation (ASIF) reported the results of a full literature review and two virtual global forum events, involving patients and patient group representatives, researchers, rheumatologists, and other healthcare professionals.* The aim was to explore key diagnosis challenges across different healthcare systems, to better understand how the delays affect individuals and to identify opportunities for addressing these.

The findings from these activities were incorporated within a new ‘Delay to Diagnosis’ report, which details the lived experiences from a global perspective of the axSpA diagnosis delay. The report identified shared issues across different countries and healthcare systems contributing to the current average global 7-year diagnosis delay. These include:
  1. poor awareness of axSpA amongst those with symptoms;
  2. lack of disease recognition amongst the wider population;
  3. incorrect diagnosis at the first point of healthcare system contact;
  4. poorly defined referral pathways;
  5. difficulties in accessing appropriate care; and,
  6. challenges within rheumatology itself.
*Webb D, et al. The Unacceptable Delay to Diagnosis in Axial Spondyloarthritis; Developing a Call to Action for a Global Healthcare Challenge. Presented at EULAR 2021; abstract OP0275-PARE.

Pregnancy outcomes are affected by both maternal and paternal inflammatory arthritis disease

Two studies presented at the 2021 EULAR annual meeting show women with rheumatoid arthritis (RA) are at increased risks of adverse pregnancy outcomes, especially pre-term birth and babies small for gestational age; and, for the first time, show that the partners of men with inflammatory arthritis have a lower rate of live births, and are more likely to suffer a miscarriage.

In the first study, Swedish and Danish researchers examined pregnancy outcomes in relation to disease activity and treatment strategies in women with RA.* Overall, women with RA had an increased likelihood of having pre-term babies (PTB) and small gestational age babies (SGA). High maternal disease activity during pregnancy strengthened the associations with both PTB and SGA. Looking at the effects of different medication treatments, researchers found combination therapy with biologics together with oral steroids and/or csDMARDs** in the 9 months before pregnancy was associated with an increased risk of PTB and SGA. During pregnancy, disease activity appears to be the most important risk factor for PTB and SGA in women with RA. The findings highlight the importance of monitoring RA during pregnancy, especially in women receiving extensive treatment, or those with continuing disease activity.

In a second study, researchers looked at the pregnant partners of men with inflammatory arthritis to determine the relationship between paternal older age, sperm DNA integrity and certain genetic defects with worse pregnancy outcomes.***

This is the largest study to describe the pregnancy characteristics and outcomes of partners of men with inflammatory arthritis, and the first to demonstrate that paternal disease is associated with a higher risk of miscarriage. However, researchers cautioned the link between disease activity, type and timing of inflammatory arthritis medication treatment, and the risk of these outcomes remains unclear and needs further study.

*Hellgren K, et al. Pregnancy outcomes in relation to disease activity and anti-rheumatic treatment strategies in women with rheumatoid arthritis - a matched cohort study from Sweden and Denmark. Presented at EULAR 2021; abstract OP0210.

**Conventional synthetic DMARDs include traditional medications such as methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, gold, salts and others.

***Perez-Garcia LF, et al. Paternal inflammatory arthritis is associated with a higher risk of miscarriages: results of a large multicenter study (iFAME-Fertility). Presented at EULAR 2021; abstract OP0211.

Decline in risk of dementia and heart failure in RA patients

Two studies from the Mayo clinic in the United States show a substantial decline in the risk of both dementia and heart failure in people with rheumatoid arthritis (RA) onset in the 2000s as compared to 1980s – coinciding with the introduction of biologic treatments for RA.

Heart failure is one of the most common cardiovascular conditions in people with RA, and previous studies have suggested that people with RA are twice as likely to develop heart failure as people in the general population without RA. For dementia, previous studies have delivered mixed results about the pattern of cognitive impairment and dementia in people with RA compared to the general population – with some showing increased odds, while others show the reverse. Furthermore, existing studies have not evaluated trends in incidence of dementia or heart failure to see if the risks have changed over time.

Mayo Clinic researchers ran population-based studies to assess the incidence of dementia or heart failure over time in people with RA, and compared to the general population.* Overall, the risk of dementia in RA patients was significantly higher than in people without RA. When subdivided by decade, the risk of dementia in people diagnosed with RA was higher than non-RA comparators in the 1980s and 1990s – but not the 2000s.

Researchers in a second Mayo Clinic study used the same methods to look at the trends of heart failure in 905 people diagnosed with RA between 1980 and 2009.** These results show there was no difference in incidence of heart failure in the 1990s and 2000s compared to the 1980s. When comparing the risk of heart failure in people with and without RA, those diagnosed with RA in the 2000s had no excess risk of heart failure compared to the general population.

Researchers observed that further studies should investigate these associations, and look at the role of inflammation, autoimmunity, and inflammatory arthritis treatments in the risk of dementia and heart failure.

*Kronzer V, et al. Trends in Occurrence of Dementia in Patients with Rheumatoid Arthritis: a Population-based Cohort Study, 1980-2009. Presented at EULAR 2021; abstract OP0216.

**Myasoedova E, et al. Decline in Excess Risk of Heart Failure in Patients with Rheumatoid Arthritis in Recent Years. Presented at EULAR 2021; abstract OP0102.