A significant indicator of whether a patient with rheumatoid arthritis will improve over the course of disease may lie in part in their gut, according to new research from Mayo Clinic’s Center for Individualized Medicine.

The study, published in Genome Medicine, found that predicting a patient’s future rheumatoid arthritis prognosis could be possible by zeroing in on the trillions of bacteria, viruses and fungi that inhabit their gastrointestinal tract, known as the gut microbiome. The findings suggest that gut microbes and a patient’s outcome of rheumatoid arthritis are connected.

“This is the first study to date that uses gut microbiome data to predict clinical improvement in rheumatoid arthritis disease activity independent of the initial measurement of their condition or prior treatment,” says Jaeyun Sung, Ph.D., a computational biologist within Mayo Clinic’s Center for Individualized Medicine and co-senior author of the study.

Rheumatoid arthritis is a chronic disorder characterized by joint inflammation and pain that can eventually lead to bone and cartilage erosion, joint deformity and loss in mobility. This complex disease affects nearly 1.3 million people in the U.S.

Zeroing in on the microbiome

For the study, the team performed a comprehensive precision genomic analysis, called “shotgun metagenomic sequencing,” on stool samples from 32 patients with rheumatoid arthritis at two separate clinical visits. The team investigated the connection between the gut microbiome and the smallest meaningful changes in clinical disease activity. The team found several traits of the gut microbiome linked to future prognosis.

“By looking at patients’ baseline gut microbiome profiles, we observed significantly different microbiome traits between patients who eventually showed improvement and those who did not,” says John M. Davis III, M.D., a clinical rheumatologist at Mayo Clinic with a specialty interest in inflammatory arthritis. Dr. Davis is co-senior author of the study.

“What was surprising is that our data suggest that depending on the eventual clinical outcome, gut microbiomes not only start at different ecological states, but also grow and develop differently,” Dr. Sung adds.

Next, by using deep-learning artificial intelligence (AI), the investigators examined if they could predict whether a patient achieves clinical improvement. Overall, the predictive performance resulted in 90% accuracy, thereby showcasing the proof of concept that the integration of gut microbiome and AI technology could theoretically be an avenue to predict disease course in rheumatoid arthritis.

Path toward treatment

“With further development, such prognostic biomarkers could identify patients who will achieve early clinical improvement with a given therapy, thereby sparing them the expense and risk of other therapies that are less likely to be effective,” Dr. Davis says. “Conversely, such tools can detect patients whose disease symptoms are less likely to improve, and perhaps allow clinicians to target and monitor them more closely. Much is left to be done, but we’re on the right path toward advancing our understanding of this disease in order to individualize medicine for patients with rheumatoid arthritis.”

Scientists have suspected for some time that the gut microbiome plays a role in rheumatoid arthritis, as well as many other inflammatory and autoimmune diseases. The enormous population of microbes help digest food, regulate the immune system and protect against pathogenic bacteria.

The researchers emphasize that every person’s microbiome is unique and consists of a complex mix of genetic, dietary and environmental influences. These differences shed light on why symptoms vary significantly among rheumatoid arthritis patients, which in turn makes it so difficult to treat and predict clinical outcome.

The study is the second recent rheumatoid arthritis investigation by Drs. Sung and Davis, highlighting the essential partnership between computational biologists and clinicians to solve complex problems in medicine. Together, they are on a path toward developing a suite of new data-driven tools to aid in early detection, diagnosis, prognosis and treatment in rheumatoid arthritis. As such, the researchers plan to explore ways to translate their findings into new biomarkers and therapies.

“Ultimately, our study reveals that modifying the gut microbiome to enhance clinical outcome may hold promise as a future treatment for rheumatoid arthritis,” Dr. Sung says. “This could revolutionize how we deliver care to our patients.”

This work was supported in part by Mayo Clinic’s Center for Individualized Medicine and Mark E. and Mary A. Davis.

Researchers from Queen Mary University of London have developed a new approach to address cardiac disease in rheumatoid arthritis (RA) patients. 

Currently patients with RA are particularly susceptible to a type of cardiac deficiency termed diastolic dysfunction, that may lead to heart failure, resulting in a higher mortality rate amongst this patient group.

The new study, published in PNAS,addresses this unmet clinical need by developing an experimental model of cardiomyopathy in inflammatory arthritis.

After several attempts the team of researchers from Queen Mary’s William Harvey Research Institute (WHRI) successfully identified the right model by characterising experimental animals with arthritis. The animals developed cardiac diastolic dysfunction, recapitulating the symptoms presented by RA patients. Diastolic dysfunction means the heart is able to contract as normal but unable to dilate properly, ultimately leading to heart failure over time.  

Professor Mauro Perretti, lead study author and Professor of Immunopharmacology at Queen Mary University of London said:  “As is often the case, the description of a valid model of disease can open new vistas on pathogenic mechanisms as well as on novel therapeutic approaches. At present, the cardiomyopathy of patients affected by rheumatoid arthritis is not treated and, on top of this, current anti-rheumatic drugs (e.g. biologics or steroids) may even worsen it. As such there is an urgent therapeutic need to intervene and treat, if not cure, the cardiomyopathy of patients affected by rheumatoid arthritis.”

“The broad area of cardiac inflammation is largely unexplored. At the WHRI we have several groups addressing experimental and translational work on several syndromes of the heart. Thus, there is work on myocarditis, on diabetes-induced cardiomyopathy and now with this study, the cardiomyopathy of inflammatory arthritis. The WHRI at Queen Mary University of London is a place of excellence to study cardiac inflammation in all its multiple faces, thanks also to our partnership with the Barts Heart Centre at Barts Health NHS Trust.”

Sitting down and listening to a patient’s story is the first step in diagnosis of Rheumatoid Arthritis. While swollen joints are a large indicator of Rheumatoid Arthritis, there are many other symptoms, such as fatigue, anxiety and depression, and stiffness. Doctors are diagnosing Rheumatoid Arthritis much earlier now, to prevent joint damage and begin treatment as soon as possible.

In a new study, researchers evaluate the similarities and differences among the disease activity indices used for patients with rheumatoid arthritis

In a new study, researchers evaluate the similarities and differences among the disease activity indices used for patients with rheumatoid arthritis CREDIT Chinese Medical Journal

Rheumatoid arthritis (RA) is an inflammatory joint disease, which when left improperly treated could result in joint deformation and functional loss. Hence, once RA is diagnosed in an individual, appropriate monitoring and treatment are the needs of the hour.

While treating patients with debilitating diseases like RA, doctors employ several established “disease activity indices” to monitor its progression and guide treatment. Such indices yield important information about patients with RA in terms of different disease ‘grades’, ranging from mild to severe activity. However, when different indices are used for one disease, they can categorize the same patient into different disease activity groups, leading to differences in treatment. Hence, although RA diagnoses are conventionally evaluated using established indices like disease activity score 28 (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI), none of these are accepted as a “gold standard”.

To understand this disparity better, a group of Chinese researchers sought to identify the correlation and concordance among the evaluated RA indices. Their pioneering study has been published in Chinese Medical Journal.

Speaking about the importance of the study, Dr. Xiao-Feng Zeng from the Department of Rheumatology, Peking Union Medical College Hospital, China, who is corresponding author of this study, says, “This is the first comprehensive comparative study of RA patients’ disease activity indices (DAIs) in China. In the future, we could accurately evaluate the epidemiology, treatment, prognosis and pharmacoeconomics of RA in China. This lays a solid foundation for the formulation of Chinese guidelines, determination of unmet clinical needs, and development of new drugs, in China.”

The researchers used information available in a big data platform for rheumatoid arthritis, called Chinese Registry of Rheumatoid Arthritis (CREDIT), from 2016 to 2018. They performed statistical analysis on the extracted data and found that of all the patients included, a staggering 80.46% were women. Further, most of the patients with RA presented with moderate-to-high disease severity.

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are known reliable indicators of possible RA inflammation. Therefore, the researchers observed high correlations among DAS28-ESR, DAS28-CRP, SDAI, and CDAI. However, though the different indices showed high levels of correlation overall, the levels of discordance among them were also significant. Hence, the researchers concluded that there is no ‘gold standard’ index, and the indices were not interchangeable.

According to the researchers, this study will definitely pave for clinicians and researchers to perform more critical analysis of RA in patients, using the various disease indices. In this regard, Dr. Zeng adds, “Through this article, the rheumatologists will learn about the differences of RA-DAIs among the Chinese patients. At the same time, we hope that Chinese experts will join or continue to cooperate with us in providing the patient information online, thus improving the CREDIT database.”