Rheumatoid arthritis (RA) treatment has improved dramatically over the past two decades as further insight has been gained into the immune pathophysiology of this chronic joint disease that affects nearly 1.5 million people in the United States. Biologic therapy, including TNF inhibitors and several non-TNF targeted biologics, has allowed physicians to intervene earlier and enabled patients to achieve quicker relief, more productive lives, and better overall outcomes.

Chinese medicine based on combinations of typically five to ten plants has a long tradition of use against rheumatoid arthritis, but few clinical trials have tested its potential. A review in the Journal of Internal Medicine outlines a strategy to analyze the ability of different mixtures of plants used in Chinese medicine to combat rheumatoid arthritis.

The strategy involves isolating the active components of individual plants and testing them alone or in combinations against key pathways of disease pathology, followed by experiments conducted in animal models of rheumatoid arthritis.

“A substantial number of our current drugs are natural products or derivatives thereof, and without doubt nature will continue to be a source of future discoveries,” the authors wrote. “Therefore continuous research based on the traditional use of plants is highly motivated. In our opinion, the strategy of starting from knowledge in traditional medicine, followed by the combination of in vivo evidence of efficacy and bioassay-guided isolation to understand the chemistry and pathways involved, is one effective way forward.”

URL : https://onlinelibrary.wiley.com/doi/10.1111/joim.13537

Pregnant women with active rheumatic disease carry a higher risk of adverse outcomes than the general population including hypertension, preeclampsia, higher cesarean section rate, small for gestational aged infants, preterm delivery, and fetal loss. To decrease the risk of these complications, rheumatic disease should be under control before conception with medications that are safe to use during pregnancy.

Those are among the findings detailed in a recent review article written by UT Southwestern physicians in Rheumatic Disease Clinics of North America.

“Rheumatologic disorders are common amongst women of reproductive age. Understanding the management of rheumatic diseases in pregnant women is an important part of patient care for rheumatologists,” said Bonnie Bermas, M.D., Professor of Internal Medicine in the Division of Rheumatic Diseases at UT Southwestern. “If we have a better understanding of pregnancy management in our patients, then we can help patients achieve their family planning goals.”

In the article, Dr. Bermas and colleagues outlined the risks of pregnancy in women with rheumatic disease and the safety of medications with pregnancy and lactation. The review focused on three diseases – rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and obstetric antiphospholipid syndrome (APS).

Each carries different risks and considerations:

• About half of RA patients experience disease remission during pregnancy. Conversely, some RA patients experience flares. Active disease prior to conception and discontinuation of RA medication is associated with RA flares during pregnancy while low disease activity prior to conception is associated with disease control.
• For many years, SLE patients were often counseled to avoid pregnancy based on concerns over increased disease activity and adverse outcomes. Poor outcomes are still seen in women with very active disease in the pre-conception period, in particular those with active renal disease. Managing renal flare during pregnancy is challenging as it is difficult to differentiate preeclampsia from an SLE flare. However, many SLE patients can have successful pregnancies with maintenance of low disease activity. Importantly, continuing hydroxychloroquine, a mainstay of therapy, improves pregnancy outcome.
• Obstetric APS is defined by three first trimester pregnancy losses, second or third trimester loss, premature delivery at less than 34 weeks, or severe preeclampsia in women who have the presence of antiphospholipid antibodies. These patients require anticoagulation and low-dose aspirin during pregnancy.

Ultimately, having the disease under good control on pregnancy-safe medication is the best path for a successful pregnancy. While some antirheumatic drugs cannot be used during pregnancy, many can.

“Our knowledge regarding the safety of medications during pregnancy is limited because pregnant women are excluded from the majority of clinical trials,” said Dr. Bermas.  Efforts over the past few years have led to the publication of guidelines on the use of medications during pregnancy and lactation in rheumatic disease. Of note, hydroxychloroquine, immunosuppressive agents such as azathioprine, cyclosporine, and tacrolimus, as well as low-dose aspirin are all safe for use during pregnancy and lactation. Pre-conception counseling with a rheumatologist knowledgeable in this area or a maternal-fetal medicine specialist is an important part of reproductive rheumatology care.

Veena Taneja, Ph.D. from the Center for Individualized Medicine, sat down to talk about the research being conducted on how the gut microbiome can lead researchers to potential treatments for Rheumatoid Arthritis.

Although interstitial lung disease (ILD) is a common manifestation of rheumatoid arthritis (RA), it is a difficult condition to diagnose. By the time ILD is visible in a CT scan, it is often at an advanced state and difficult to treat. 

Fan Zhang, PhD, an assistant professor of rheumatology in the University of Colorado School of Medicine, recently received a grant from the PhRMA Foundation for her research aimed at finding an approach to diagnose and treat RA-associated ILD earlier.

Using machine learning — computer systems that use algorithms and statistical models to analyze and draw inferences from patterns in high-dimensional data — she plans to analyze millions of single cell profiles from the joint and lung tissue of patients with RA and ILD to see if there are common connections between the two. The Zhang lab research takes place through the CU School of Medicine as well as the Center for Health AI (Artificial Intelligence) on the CU Anschutz Medical Campus. 

 “By comparing the cell profiles between those two tissues, we will be able to predict the shared pathogenic features,” Zhang says. “They could be genes, transcriptional factors, or migrating molecules. We hope to reveal novel non-invasive ways to identify progressive RA-ILD through identification of markers in blood, as well as potential transcriptional regulators that drive the inflammatory cell populations. These can be further targeted to stop inflammation in patients with RA.” 

The joint-lung connection 

ILD is characterized by progressive scarring of lung tissue that affects a person’s ability to breathe and get enough oxygen into their bloodstream. For many, the damage is irreversible, though medications can slow it down. In people with RA, ILD is a leading cause of morbidity and mortality, detected in up to 60% of patients. RA patients with ILD have three times the risk of death compared to those without the disease. 

Zhang’s research looks specifically at myeloid cells, a major source of cytokines that play an important role in tissue inflammation in RA. Her previous studies of RA and RA-ILD lung disease revealed a shared myeloid population that may represent a key pathogenic population linking these two inflamed tissues, highlighting the need for a greater understanding of the pathogenic connections between the joint and lung.  

“With this grant, we are using the theory of system biology and machine learning to help with translational medicine,” Zhang says. “An improved understanding of the mechanisms that underlie rheumatoid arthritis targeting the joint-lung axis and tissue-blood comparison may help develop therapies to better treat rheumatic diseases in the future.”  

Personalized solutions for autoimmune conditions 

The Zhang lab has related research funding through the Accelerating Medicines Partnership — a public-private partnership between the National Institutes of Health, the U.S. Food and Drug Administration, and pharmaceuticals companies — targeted at autoimmune and immune-mediated diseases. Since this is a new area of study, Zhang hopes to build a collaborative team of computational biologists and postdocs to join her to work on this single-cell translational medicine project.

“I feel like there is a need to identify a precision medicine for autoimmune disease, because there are no effective personal treatments currently,” she says. “I think we can use big data to looking at patient cells and more effectively identify accurate targets.”