Rheumatoid arthritis is a chronic inflammatory disorder marked by joint pain, swelling and damage. Although medications, such as steroids, anti-inflammatory drugs and immunosuppressants, can help slow joint destruction and relieve pain, they have side effects and aren’t completely successful. Now, researchers reporting in ACS’ Nano Letters have developed magnesium-based micromotors propelled by hydrogen bubbles, which improved rheumatoid arthritis symptoms when injected into the joints of rats.

Scientists have linked rheumatoid arthritis development to the excess production of reactive oxygen species (ROS). ROS can oxidize and degrade cartilage and bone, as well as activate the expression of inflammatory cytokines. A new type of therapy, hydrogen gas, can neutralize ROS and decrease inflammatory cytokine levels when given to patients in drinking water. However, the gas is poorly soluble in body fluids and quickly eliminated when given orally, limiting its therapeutic effects. Fei Peng, Yingfeng Tu, Yingjia Li and colleagues wanted to find a way to produce and deliver hydrogen gas directly inside an inflamed joint.

The researchers based their system on magnesium-based micromotors –– tiny spheres that react with water to produce hydrogen bubbles, which propel the motors. They coated the micromotors with hyaluronic acid, a joint lubricant, leaving a small opening for the magnesium to react with water. When placed in simulated joint fluid, the micromotors showed prolonged, sustained release of hydrogen bubbles and could move on their own. The team then injected the micromotors into the joints of rats that served as an animal model of rheumatoid arthritis and used ultrasound to visualize them. Compared with uninjected rats, the treated rats showed less-swollen paws, reduced bone erosion and lower levels of inflammatory cytokines. Although the micromotors still need to be tested in humans, they show great potential for the therapy of rheumatoid arthritis and other inflammatory diseases, the researchers say.

Treatment 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.

Other study authors are Paul Tak M.D, Ph.D., University of Amsterdam; Ronald Van Vollenhoven, M.D., Ph.D., University of Amsterdam; Leonid Padyukov, M.D., Ph.D., Karolinska Institutet; Paul Emery, M.D., University of Leeds; Ann Morgan, M.B., Ch.B., Ph.D., University of Leeds; Tim Bogartz, M.D., Vanderbilt Medical Center; Arjun Athreya, Ph.D., Mayo Clinic; Erin Carlson, Mayo Clinic; Cynthia Crowson, Ph.D., Mayo Clinic; John Davis III, M.D., Mayo Clinic; Kenneth Warrington, M.D., Mayo Clinic; Krishna Kalari, Ph.D., Mayo Clinic; Robert Walchak, Mayo Clinic; Richard Weinshilboum, M.D., Mayo Clinic; Liewei Wang; M.D., Ph.D., Mayo Clinic; and Eric Matteson, M.D., Mayo Clinic.

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.

Any impact is small and not clinically meaningful; and too few high quality dietary studies

Diet is unlikely to make any difference to the progression of osteoarthritis and rheumatoid arthritis, finds a review of the existing scientific evidence, published in the open access journal RMD Open.

While a healthy diet brings other health benefits, any impact on rheumatoid and musculoskeletal diseases is small and not clinically meaningful, but there just aren’t enough high quality dietary studies, the review concludes.

Diet is known to influence cardiovascular and mental health outcomes, but it’s not clear whether it might also influence the symptoms and progression of rheumatic and musculoskeletal diseases.

In a bid to find out, the European League Against Rheumatism (EULAR) convened an international taskforce in 2018 to look at the potential impact of diet, exercise, weight, alcohol, smoking and paid work on disease progression, and develop appropriate recommendations for clinicians and patients for each of these behaviours. 

For the dietary recommendations, the taskforce searched for relevant systematic reviews of randomised controlled trials or observational studies and pooled data analyses looking at the impact of dietary components/supplements on pain, joint damage, and physical function for seven common rheumatoid and musculoskeletal conditions.

These were: osteoarthritis; rheumatoid arthritis; systemic lupus erythematosus; axial spondyloarthritis; psoriatic arthritis; systemic sclerosis; and gout.

In all, 24 systematic reviews, published between 2013 and 2018, and 150 original research articles with no restriction on publication date, were included in the pooled data analysis 

Most of the studies concerned osteoarthritis and rheumatoid arthritis and featured a wide range of dietary compounds/supplements: animal products; experimental diets; food components; fruit and veg plus other plant-based interventions; minerals and supplements; and vitamins.

There were relatively few dietary studies for osteoarthritis, meaning that the evidence for these was graded as poor or very poor. 

The pooled data analyses showed that for dietary interventions with moderate evidence (fish oil, chondroitin, glucosamine, vitamin D, avocado and soybean), the magnitude of the impact on disease progression was generally small and not clinically meaningful.

The evidence for most dietary interventions in rheumatoid arthritis was graded as poor or very poor, primarily because of the small number of studies and participants. There was moderate quality evidence  for probiotics, vitamin D, fish oil/omega-3 but the impact was either negligible or too small to make much difference.

The evidence for fish oil/omega-3 for systemic lupus erythematosus was rated as moderate but showed no effect on outcomes. The evidence for all other studies on this condition was rated as poor or very poor, as it was for axial spondyloarthritis.

Similarly, the evidence for fish oil/omega-3 for psoriatic arthritis was rated as moderate and showed no effect on outcomes. The evidence for other dietary interventions was rated as poor. The evidence for systemic sclerosis and gout was also rated as poor.

“Therefore, based on the current evidence, there is no single dietary intervention which has substantial benefits on the outcomes of people with [osteoarthritis and rheumatoid arthritis],” conclude the authors. 

“While there have been far fewer research studies published for the other included [rheumatic and musculoskeletal diseases], again, there is no consistent evidence that any dietary exposure significantly improves outcomes in these conditions,” they add.

While diet might not make much difference to disease progression in these conditions, those who live with them should nevertheless make sure they eat healthily and don’t put on too much weight, they emphasise.

“Health professionals can advise people with [these conditions] that consuming specific dietary components is unlikely to influence the progression of their [disease], but that it is important to maintain a healthy diet and healthy weight for general health reasons,” they write. 

Dr. Bartlett shares a recent research update on fatigue and Rheumatoid Arthritis.