Tag: rheumatoid arthritis

Treatment of Rheumatoid Arthritis Before Disease Develops Yields Benefits

Hand osteoarthritis
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A temporary treatment with methotrexate in the early stages of rheumatoid arthritis resulted in benefits for patients, according to research published in The Lancet. By temporarily prescribing methotrexate in the “pre-rheumatic phase,” patients experienced a reduction long-term joint inflammations, pain and physical limitations.

“At present, methotrexate is only prescribed to the patient following a rheumatoid arthritis diagnosis,” explained Annette van der Helm, Professor of Rheumatology at Leiden University Medical Centre. “But that is too late. By then, the disease is already considered chronic.” The researchers hope to prevent or reduce disease burden by giving methotrexate to patients likely to develop rheumatoid arthritis.

The researchers found that while the development of rheumatoid arthritis was not prevented by early treatment, diagnosis was delayed. Patients that had temporarily received methotrexate also reported less pain, morning stiffness and daily functioning impediments. Fewer joint inflammations were seen in MRI scans. “This is an important step towards reducing disease burden for this group of patients,” said Prof Van der Helm. “Moreover, it serves as initial evidence for initiating treatment in the ‘pre-rheumatic’ phase.”

The 8 year study included more than 230 patients. “All suffered from joint pain and inflammation, which could be seen on the MRI, and was thought to be a rheumatism precursor,” said PhD student Doortje Krijbolder. Rheumatologists are not certain whether this is truly the case, however. Pre-rheumatoid patients were treated with methotrexate or a placebo for one year, and a one year follow-up enabled researchers to see if the effects of the treatment persisted.

“This chronic disease is extremely burdensome to patients and their families. Our study is paving the way toward arthritis prevention,” said Prof Van der Helm. “To achieve this completely, greater understanding of the molecular processes underlying the chronic nature of rheumatoid arthritis is necessary.”

Source: Medical Xpress

New AIRD Therapies Could Cut Side-effects

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New therapies for autoimmune rheumatic diseases (AIRDs) that are designed to better regulate lipid metabolism could significantly reduce the harmful side-effects caused by conventional treatments, researchers found in a new large-scale review.

AIRDs include rheumatoid arthritis, lupus and Sjögren’s syndrome – conditions which affect millions and all with high rates of morbidity. The pathogenesis of autoimmune conditions is still ill-defined and delivering targeted therapeutic strategies is challenging.

As a result, current treatments for AIRDs are primarily designed to suppress the symptoms (inflammation), but are ‘low target’, ie may also have unintended side-effects. In this regard, AIRDs drugs often cause changes to cell metabolism (such as lipid metabolism) and function, putting patients at greater risk of co-morbidities such as cardiovascular disease (CVD).

Lead author Dr George Robinson (Centre for Rheumatology Research, UCL Division of Medicine) said: “While the mechanisms that cause rheumatic diseases are ill-defined, some recent research indicates cell metabolism may play an important role in triggering or worsening their onset or affect.

“In this review we therefore sought to understand the effect of both conventional and emerging therapies on lipid metabolism in patients with AIRDs.”

For the study, published in the Journal of Clinical Investigation, researchers reviewed more than 200 studies to assess and interpret what is known regarding the on-target/off-target adverse effects and mechanisms of action of current AIRD therapies on lipid metabolism, immune cell function and CVD risk.

Explaining the findings, Dr Robinson said: “Our review found that current AIRD therapies can both improve or worsen lipid metabolism, and either of these changes could cause inflammation and increased CVD risk.

“Many conventional drugs also require cell metabolism for their conversion into therapeutically beneficial products; however drug metabolism often involves the additional formation of toxic by-products, and rates of drug metabolism can be different between patients.”

The review noted that optimal combinations of immunosuppressive treatments to better control inflammation could lead to an improved metabolic/lipid profile in AIRDs.

However, many studies also showed that lipid lowering drugs such as statins do not sufficiently lower CVD risk in some AIRDs, possibly because they cannot completely restore the anti-inflammatory properties

Dr Robinson added: “The unfavourable off-target adverse effects of current therapies used to treat AIRDs provides an opportunity for optimal combination co-therapies targeting lipid metabolism that could reduce immune complications and potential increased CVD risk in patients.

“New therapeutic technologies and research have also highlighted alternative metabolic pathways that can be more specifically targeted to reduce inflammation but also to prevent undesirable off-target metabolic consequences of conventional anti-inflammatory therapies.”

Source: University College London

Why Does Arthritis Flare Up in the Same Place?

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A new study has revealed why arthritis has a tendency to flare up in the same location instead of around the body.

When joints flare up in people with rheumatoid arthritis and related diseases, the joints involved are often the same as those previously affected. For example, if arthritis started in the right knee, it is much more likely to flare there than in the left knee, even if the arthritis had been in remission for years. Because of this, each patient develops a highly individual disease pattern, though why this is so has remained unclear.

“Overwhelmingly, flares occur in a previously involved joint,” said Peter Nigrovic, MD, chief of the division of immunology at Boston Children’s Hospital. “Something in that joint seems to remember, ‘this is the joint that flared before.’”

A new study, co-led by Dr Nigrovic and published in Cell Reports, shows where that memory is housed: in a type of immune cell called a tissue-resident memory T cell. Specifically, these T cells reside in the synovium, the tissue that lines the inside of the capsule surrounding the joint.
“We showed that these T cells anchor themselves in the joints and stick around indefinitely after the flare is over, waiting for another trigger,” said Dr Nigrovic. “If you delete these cells, arthritis flares stop.”

The team demonstrated this phenomenon in three separate mouse models of inflammatory arthritis. Two models used chemical triggers to cause joint inflammation, and the third had a protein knocked out that blocks the pro-inflammatory cytokine IL-1. Once activated, resident memory T cells in the joints rallied other immune cells, leading to an arthritis flares limited to specific joints. Elimination of these T cells prevented further flares from occurring.

“Right now, treatment of rheumatoid arthritis has to continue lifelong; although we can successfully suppress disease activity in many patients, there is no cure,” said Dr Nigrovic. “We think our findings may open up new therapeutic avenues.”

Dr Nigrovic also believes the findings apply to other types of autoimmune arthritis, including juvenile idiopathic arthritis.

Dermatology provided a cue for the researchers: tissue-resident memory T cells were originally found in skin, where a ‘memory’ pattern is well known to dermatologists. In psoriasis, for example, patients get recurrent plaques in the same places. The same often holds true in cutaneous hypersensitivity reactions, such as reactions to nickel in jewelry or wristwatches. “A person reacting to nickel through a belt buckle may also develop a rash on their wrist, where they wore a nickel-containing watch as a child,” observed Dr Nigrovic.

Source: EurekAlert!

New Approach to Address Cardiac Disease in Rheumatoid Arthritis

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A new approach to address cardiac disease in rheumatoid arthritis (RA) patients has been developed.

Currently patients suffering from RA are also particularly susceptible to diastolic dysfunction, a type of cardiac deficiency which may lead to heart failure, resulting in a higher mortality rate among such patients.
To address this unmet clinical need, researchers from Queen Mary’s William Harvey Research Institute (WHRI) responded by developing an experimental model of cardiomyopathy in inflammatory arthritis.

After several attempts, the researchers finally hit upon 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 (eg 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.”

The study was published in PNAS.

Source: EurekAlert!

Parental Smoking Linked to Children’s Later Arthritis

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In a new study, parental smoking was linked to an elevated risk of children developing rheumatoid arthritis when they reach adulthood.

Drawing on data for 90 923 participants in the Nurses’ Health Study II (which included female registered nurses aged 25–42 years in 1989), the researchers found that 532 developed rheumatoid arthritis during a median follow-up of 27.7 years. Parental smoking when the participants were children was associated with a 75% higher risk of developing rheumatoid arthritis, even after controlling for personal smoking when the participants were adults. Among participants who went on to smoke as adults, this risk was even greater.

“These results suggest that early life inhalant exposures such as passive smoking may predispose individuals to develop rheumatoid arthritis later in life,” said senior author Jeffrey A. Sparks, MD, MMSc, of Brigham and Women’s Hospital.

“We used advanced statistical methods that allowed us to decipher the potential direct harm of early-life passive smoking experience on rheumatoid arthritis risk, while also taking into account factors occurring throughout adulthood,” added lead author Kazuki Yoshida, MD, ScD.

The study findings were published in Arthritis & Rheumatology.

Source: Wiley

Bacteria in the Mouth Linked to Arthritis

A dentists shows her patient some dental X-rays. Photo by Tima Miroshnichenko from Pexels

Researchers found similar oral bacterial compositions among patients with early rheumatoid arthritis and those at risk of developing the disease, compared with healthy individuals who were not at risk.

The oral cavity is host to approximately 800 identified species of bacteria. The periodontum, ie the tissue surrounding the tooth, can become inflamed because of a complex interaction of bacterial infection and the body’s response, modified by behavioural factors such as smoking, result in periodontal disease. Periodontal disease has been shown to be caused by certain diseases and medical conditions, and may also cause them. Periodontitis is prevalent among rheumatoid arthritis patients. 

The researchers recruited three groups of 50 participants each: early rheumatoid arthritis patients, at‐risk individuals, and healthy controls. They were given periodontal examinations and assessed for bleeding on probing, pocket probing depth, and periodontal inflamed surface area. The microbial composition of subgingival dental plaque, saliva, and tongue coating was assessed using 16S rDNA amplicon sequencing, and compared between groups.

They found that patients and at-risk individuals had an increased relative abundance of potentially pro- inflammatory bacteria in the mouth, suggestive of a possible relationship between oral microbes and rheumatoid arthritis.

“Prevotella and Veillonella–both gram-negative anaerobes–were at higher relative abundance in saliva, and Veillonella was also at higher relative abundance in tongue coating, of both early rheumatoid arthritis patients and at-risk individuals compared to healthy controls,” the authors wrote.

The findings were published in Arthritis & Rheumatology.  

Source: News-Medical.Net

Journal information: Kroese, J. M., et al. (2021) The oral microbiome in early rheumatoid arthritis patients and individuals at risk differs from healthy controls. Arthritis & Rheumatology. doi.org/10.1002/art.41780.