Third Grader Grace Moyers shares the early journey she’s had living with Juvenile Rheumatoid Arthritis.
Can you believe I have rheumatoid arthritis? | Grace Moyers
Rheumatoid arthritis
Researchers link gut microbiome to rheumatoid arthritis prognosis
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.”
Rheumatoid Arthritis Flares: Tips on Self-managing a RA Flare | Johns Hopkins Medicine
Dr. Uzma Haque goes over some self-management techniques to help alleviate the symptoms of a flare.
Mayo Clinic researchers use AI, biomarkers to personalize rheumatoid arthritis treatment
reatment options for rheumatoid arthritis have often relied on trial and error. Now Mayo Clinic researchers are exploring the use of artificial intelligence (AI) and pharmacogenomics to predict how patients will respond to treatments, and to personalize care. Findings were published in Arthritis Care & Research.
The study focused on predicting the response to methotrexate, one of the most common rheumatoid arthritis medications. Applying patient data that included genomic, clinical and demographic information, researchers used AI to determine an initial response to methotrexate in patients with early-stage rheumatoid arthritis. Data used in the study came from a collaboration between Mayo Clinic and the Pharmacogenetics of Methotrexate in Rheumatoid Arthritis (PAMERA) consortium, that led to early genome-wide association studies.
This work evolved from the union of AI and pharmacogenomics co-led by Liewei Wang; M.D., Ph.D., Arjun Athreya, Ph.D. and Richard Weinshilboum, M.D. “This approach began by developing tools to predict drug treatment outcomes in major depressive disorder, but we are delighted to see that it can potentially be applied widely, in this case to the drug therapy of rheumatoid arthritis,” says pharmacogenomics leaders Drs. Wang and Weinshilboum.
“In my everyday practice, patients frequently ask, ‘What medication will be most effective for me’ or ‘What is the chance this medication will help?’ This is a study that seeks to address these questions,” says Elena Myasoedova, M.D., Ph.D., a Mayo Clinic rheumatologist and lead author. By predicting a response to methotrexate, researchers identified which patients are most likely to benefit from this medication in the first three months of treatment.
More research is needed to understand how these findings can be used in practice. The study, which is part of a series looking at the roles of AI and pharmacogenomics in treating rheumatoid arthritis, was performed in collaboration with Mayo Clinic’s Center for Individualized Medicine.
“Predicting a response to rheumatoid arthritis medication can be challenging, but this approach is very promising and is an exciting development in treating the disease,” Dr. Myasoedova says.
Hydroxychloroquine Not Linked to Longer Heart Rhythm Intervals in Rheumatoid Arthritis or Lupus Patients
New research presented at ACR Convergence, the American College of Rheumatology’s annual meeting, discovers that use of hydroxychloroquine, a generic drug, does not cause any significant differences in QTc length or prolonged QTc, key measures of heart rate, in people with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) (abstract #0431).
Rheumatoid arthritis is the most common type of autoimmune arthritis. It is caused when the immune system (the body’s defense system) is not working properly. RA causes pain and swelling in the wrist and small joints of the hand and feet. SLE is a chronic disease that causes systemic inflammation which affects multiple organs.
Hydroxychloroquine is a cornerstone treatment for SLE, and patients with RA may also take the drug either alone or in combination with other treatments. However, there are concerns about its possible heart-related side effects: the prolongation of QTc, or the time span the heart takes to contract and relax, and the development of arrhythmia (irregular heartbeats). This new study assessed QTc lengths in patients with RA and SLE and its association with hydroxychloroquine use.
“Hydroxychloroquine remains the foundation of disease-modifying antirheumatic drug therapy in rheumatic disease patients. Given recent concerns surrounding hydroxychloroquine’s use in COVID-19 patients and subsequent arrhythmic events, we wanted to examine the associations between its use and the QTc length on electrocardiograms in a large, asymptomatic cohort of RA and SLE patients,” says study co-author Elizabeth Park, MD, Rheumatology Fellow at Columbia University Irving Medical Center.
The study analyzed data on 681 RA and SLE patients without clinical cardiovascular disease, including two prospective RA cohorts of 307 patients and a retrospective SLE cohort of 374patients, that included electrocardiogram (EKG) results. The researchers explored the association between QTc length and hydroxychloroquine use by these patients, and they adjusted the data for disease-specific characteristics and cardiovascular disease (CVD) risk factors. Of the whole study group (RA and SLE), 54% used hydroxychloroquine and 44% had QTc lengths of more than 440 milliseconds. They found that the adjusted QTc length among hydroxychloroquine users was comparable to those who did not use the drug.
Their results also showed that hydroxychloroquine use did not significantly predict prolonged QTc for either the whole cohort or the RA and SLE patient cohorts. However, nine out of 11 of the SLE patients who did have a prolonged QTc were taking hydroxychloroquine. Yet these observations were too small to detect statistically significant differences between the hydroxychloroquine groups.
Prolonged QTc, or more than 500 milliseconds, was not associated with arrhythmias or deaths among these patients. The study also did not find any significant interactions between hydroxychloroquine and other QTc-prolonging medications in the patients. Hydroxychloroquine use combined with other QTc-prolonging medications resulted in a comparable QTc interval to hydroxychloroquine alone. In the SLE group, hydroxychloroquine combined with anti-psychotic drugs did result in longer QTc compared to using hydroxychloroquine alone, however.
“Overall, the use of hydroxychloroquine did not predict QTc length, even while adjusting for critical confounding factors, namely the use of other QTc-prolonging medications,” says Dr. Park. “Our findings reinforce the fact that hydroxychloroquine remains a safe, effective long-term disease-modifying drug for our rheumatic disease patients. It’s important to remember that COVID-19 patients who received hydroxychloroquine were likely critically ill. Therefore, the effect of COVID-19 itself on the heart and subsequent arrhythmia must be considered. They also likely concurrently received azithromycin, another QTc-prolonging medication. Our next steps are to stratify data by length and cumulative dose of hydroxychloroquine therapy and analyze the associations with QTc length.”