A new study, funded by a grant from the National Institute for Arthritis and Musculoskeletal and Skin Diseases (NIAMS), found that two in five adults (42%) with rheumatoid arthritis (RA) were inactive. Taking measures to motivate RA patients to increase their physical activity will improve public health according to the findings now available in Arthritis Care & Research, a journal published by Wiley-Blackwell on behalf of the American College of Rheumatology (ACR).

The ACR estimates nearly 1.3 million adults in the U.S. are diagnosed with RA, a chronic autoimmune condition characterized by systemic joint inflammation that can damage joints, impair function, and cause significant disability. Until the early 1980s, medical experts recommended medication and rest for those with arthritis. However, current medical evidence now suggests that regular, moderate physical activity benefits arthritis sufferers by maintaining joint flexibility, improving balance, strengthening muscles, and reducing pain.

“While there is much evidence of the benefits of physical activity, RA patients are generally not physically active, and physicians often do not encourage regular physical activity in this patient population,” explains Dr. Jungwha Lee, an Assistant Professor in the Department of Preventive Medicine at Northwestern University Feinberg School of Medicine in Chicago, Illinois. “Our study aims to expand understanding of the risk factors associated with inactivity among adults with RA and encourage clinical interventions that promote participation in physical activity.”

Dr. Lee and colleagues analyzed data on 176 RA patients, 18 years of age or older enrolled in a randomized controlled trial to assess the effectiveness of an intervention promoting physical activity. The team evaluated pre-intervention data for inactivity which was defined as no sustained 10-minute periods of moderate-to-vigorous physical activity during a week. Researchers also assessed the relationships between inactivity and modifiable risk factors such as motivation for physical activity, obesity, and pain.

Results show that 42% of RA patients were inactive; participating in no moderate-to-vigorous physical activity periods of at least ten minutes during a 7-day period of objective activity monitoring. Researchers found that 53% of study participants lacked strong motivation for physical activity and 49% lacked strong beliefs in the benefits of physical activity. These two modifiable risk factors account for 65% of excess inactivity in this study group.

While previous research relied on self-reported physical activity measures, the strength of the current study lies in the use of accelerometers—a device used to measure acceleration and movement—to objectively assess physical activity in participants. “Physical inactivity among RA patients is a public health concern,” concludes Dr. Lee. “Our results suggest that public health initiatives need to address the lack of motivation to exercise and promote the benefits of physical activity to reduce the prevalence of inactivity in those with RA.”

People with rheumatoid arthritis are at a greater risk of irregular heart rhythm (known as atrial fibrillation) and stroke compared with the general population, finds a study published on bmj.com today.

Rheumatoid arthritis is already linked to an increased risk of heart attacks and heart failure, and is an important risk factor for stroke. But no study has yet examined whether it increases the risk of atrial fibrillation – a condition associated with an increased long term risk of stroke, heart failure, and death.

So a team of researchers set out to examine the risk of atrial fibrillation and stroke associated with rheumatoid arthritis in the Danish population.

The study involved more than four million people, of which 18,247 had a diagnosis of rheumatoid arthritis. Participants were followed up for an average of five years, during which time cases of atrial fibrillation and stroke were recorded.

The results show that patients with rheumatoid arthritis had a 40% increased risk of atrial fibrillation compared with the general population (8.2 and 6 events per 1,000 person years respectively) with women at slightly higher risk than men. This corresponds to one new case of atrial fibrillation per 12 rheumatoid arthritis patients followed for 10 years after diagnosis.

Patients with rheumatoid arthritis also had a 30% increased risk of stroke compared with the general population (7.6 and 5.7 events per 1,000 person years respectively).

New guidelines recommend annual screening for cardiovascular risk factors in patients with rheumatoid arthritis, and this should include screening for atrial fibrillation, say the authors.

They also suggest that, as inflammation plays a role in the development of atrial fibrillation and stroke, inflammation control is crucial for patients with rheumatoid arthritis, “not only for the management of joint symptoms, but also to reduce the need for drugs with potential adverse cardiovascular effects and, ultimately, to diminish the inflammation driven atherothrombotic process.”

 Predicting the future may be beyond our grasp, but what about predicting disease progression? Researchers in Japan have delved into the human genome to investigate a predictive tool for the progression of rheumatoid arthritis (RA), an inflammatory autoimmune disease showing progressive joint damage.   

In a new study published in Arthritis & Rheumatology, researchers led by Tokyo Medical and Dental University (TMDU) used data from a genome-wide association study (GWAS) of RA susceptibility to construct a polygenic risk score (PRS). They evaluated the PRS’s ability to predict radiographic progression—progressive anatomical damage assessed by radiographic imaging—in individuals with RA. 

In a GWAS, genomic analysis of a group of individuals is performed to identify genetic variants that may be associated with a certain trait or disease. A PRS can be generated from a GWAS dataset and represents an individual’s risk of developing a specific disease based on a summation of the genetic variants associated with that disease. Previous studies have identified genetic factors associated with radiographic progression of RA, including the presence of anti-citrullinated protein antibodies (ACPAs) and variants located in the human leukocyte antigen (HLA) region of the human chromosome that contribute to regulating the immune system. However, the predictive accuracy of these factors is not robust. Therefore, the TMDU-led research team set out to evaluate the ability of the PRS to predict radiographic progression in people with RA. 

“We generated the PRS using summary statistics from a GWAS analysis of RA susceptibility and evaluated radiographic joint damage retrospectively from patient medical records,” explains lead author Suguru Honda.

The researchers then conducted statistical analysis to assess whether there is an association between PRS and severity of radiographic progression. Additionally, the research team performed a multivariable analysis to evaluate the association between radiographic progression and the combination of PRS and other factors such as sex, age of onset, and presence of ACPAs or HLA region variants.  

“Our analyses revealed an association between PRS and radiographic progression,” says senior author Yuta Kochi. “The PRS significantly differed between severe and non-severe progression groups.”
 

The researchers found that patients with a higher PRS had a higher risk of severe progression, particularly among younger-onset individuals. Furthermore, the multivariable analysis revealed that the association of the PRS with radiographic progression is not influenced by other clinical factors. Thus, PRS’s could be used to predict radiographic progression. These findings highlight the potential applications of genetic profiling in the development of precision medicine approaches for the treatment of RA.  

According to a study presented at EULAR 2012, the Annual Congress of the European League Against Rheumatism, patients with rheumatoid arthritis (RA) who are prescribed biologic treatments have a significantly lower mortality risk (adjusted hazard ratio [HR]: 0.61) than those just treated with traditional disease modifying anti-rheumatic drugs (DMARDs).The study also found the mortality was similar irrespective of the method of action of biologics (anti-tumour necrosis factor drugs [anti-TNFs] or rituximab).

Results of the German study of 8,908 patients demonstrated that the mortality rate decreased from 20.6 in those treated with non-biologic DMARDS to 10.6 in those exposed to anti-tumour necrosis factor (anti-TNFs) drugs, and likewise to 12.7 for those treated with rituximab.

Further analyses showed that men and women with RA had a shortened life expectancy of 2.2 years compared to the general population. Patients with a mean DAS28* below 4.1 had normal life expectancies whereas of patients with a mean DAS28 score of >4.1 women died 5.6 years earlier than age and sex matched subjects from the general population, whilst males died 4.8 years earlier.

“It is well-known that patients with RA have lower life expectancies than the general population,” said Dr. Joachim Listing, German Rheumatism Research Centre Berlin, Germany and lead study author. “Our study demonstrates the positive impact that biologic treatment can have on patient’s life expectancy.

According to the researchers, a significant association between disease activity and mortality risk was observed by multivariate Cox regression within the patient sample. Cox proportional hazard regression was applied to investigate the influence of the time varying DAS28 scores, functional capacity and treatments on mortality risk after adjustment for age, sex, eight co-morbid conditions and smoking. The primary analysis was based on a risk window approach assuming the patient was exposed to biologic DMARD treatment up to six months (12 months for rituximab) after the last dose. Mean observation time was 3.5 years.

Results of a separate study show that early remission is associated to better overall survival.

Results of a large observational study presented at EULAR show early and sustained remission are associated with a decreased all-cause mortality in patients in inflammatory polyarthritis. The analyses from the Norforlk arthritis register, a large population-based inception cohort of inflammatory polyarthritis established in 1990, showed that achieving remission at least once within the first three years of follow-up was associated with improved survival (adjusted HR=0.75 (0.59, 0.95), 95% CI). Number of times in remission was also associated with decreased all-cause mortality. Patients who were in remission for one year after their first assessment had the greatest reduction in mortality risk compared to patients who didn’t achieve remission within the first three years (adjusted HR=0.66 (0.47, 0.92)), while patients who achieved remission at year two or three showed a progressive loss of the beneficial effect of achieving remission. This indicates that achieving remission at an early stage in the disease process is essential to improving outcome for patients with polyarthritis.