Tag: rheumatoid arthritis

Categories : Immune SystemTags :

Immunomodulatory Rheumatoid Arthritis Drugs might Prevent Autoimmune Thyroid Disease

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Anti-rheumatic drugs used for rheumatoid arthritis (RA) might prevent the development of autoimmune thyroid disease, according to a new observational study by researchers from Karolinska Institutet which is published in the Journal of Internal Medicine.   

Patients with RA at increased risk of autoimmune thyroid diseases such as Hashimoto’s disease and Graves’ disease. While patients with RA are usually treated with immunomodulatory drugs that affect the immune system, such drugs are rarely used in autoimmune thyroid diseases. Instead, such patients are treated with thyroid hormones such as levothyroxine to compensate for the changes in normal thyroid function that accompany autoimmune thyroid disease.  

In this study, the researchers wanted to investigate whether immunomodulatory drugs that reduce inflammation in the joints of patients with RA might also reduce the risk of these patients developing autoimmune thyroid disease. Previous studies in mice suggest that so-called DMARDs, a type of immune-modulatory drugs used to treat rheumatoid arthritis, can reduce inflammation in the thyroid gland. Still, knowledge of whether this effect also applies to humans is limited, according to the research team.   

The researchers used data between 2006 and 2018 on over 13 000 patients with rheumatoid arthritis and their treatment, as well as data from over 63 000 individuals in a matched control group without rheumatoid arthritis.  

The researchers found that the risk of developing an autoimmune thyroid disease among RA patients was lower after their onset of the rheumatic disease than before diagnosis.  

The most greatest risk reduction was seen in RA patients treated with immunomodulatory drugs or ‘biological DMARDs’. In these patients, the risk of autoimmune thyroid disease was 46% lower than in the control group without rheumatoid arthritis.   

“These results support the hypothesis that certain types of immunomodulatory drugs could have a preventive effect on autoimmune thyroid disease,” says Kristin Waldenlind, researcher at the Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, specialist in rheumatology at Karolinska University Hospital and first author of the study. She continues:  

“Our results do not prove that it is the treatment with immunomodulatory drugs that led to the reduced risk of autoimmune thyroid disease, but provide support for this hypothesis. The results, if they can be replicated in further studies, open up the possibility of studying more directly in clinical trials whether the immunomodulatory drugs currently used for rheumatoid arthritis could also be used for the early treatment of autoimmune thyroid disease, ie for new areas of use of these drugs, known as drug repurposing.”

Source: Karolinksa Institutet

Categories : Ageing Immune SystemTags :

New Approach May Take the Guesswork out of Selecting Treatments for RA

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New research reported in the journal Nature could lead to new targeted treatments for rheumatoid arthritis (RA). The findings showed that guesswork could be taken out of selecting treatments for each patient, and this might one day also be extended to other autoimmune conditions.

The study was led by University of Colorado School of Medicine faculty members Fan Zhang, PhD, and Anna Helena Jonsson, MD, PhD. The Accelerating Medicines Partnership: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP: RA/SLE) Network collected inflamed tissue from 70 patients with RA from across the country and the United Kingdom. Jonsson supervised the team of scientists who processed these samples for analysis, and Zhang led the computation analysis of the data. These efforts yielded a cell atlas encompassing more than 300 000 cells from synovial tissue. Further analysis revealed that there are six different subgroups of RA based on their cellular makeup.

“We hope the data will help us discover new treatment targets,” says Jonsson, assistant professor of rheumatology. “We wanted to make it public so that researchers across the country and across the world can continue working on new treatment ideas for rheumatoid arthritis going forward.”

No more guess-and-check

Jonsson, a practicing rheumatologist as well as a researcher, knows that RA patients respond differently to different treatments. Until now, she says, rheumatologists used a “guess and check” method to find a treatment that works for an individual patient.

With the new data and powerful computational classification methods developed by Zhang and the computational analysis team, the researchers were able to quantitatively classify RA types into what they call ‘cell-type abundance phenotypes’, or CTAPs. Developed methods, together with the new cell atlas, can start to identify which patients will respond to which treatments.

“Even when you classify rheumatoid arthritis inflammation using these simple markers – T cell markers, B cells, macrophages and other myeloid cells, fibroblasts, endothelial cells – what we found is that each of those categories is associated with very specific kinds of pathogenic cell types we’ve already discovered,” Jonsson says. “Previous rheumatoid arthritis research found that T cell populations called peripheral helper T cells are relevant in rheumatoid arthritis, as are B cells called antibody-producing B cells, and other specific cell types. What we found is that they’re usually not found all together.

“For example, the peripheral helper cells are found with the B cells in only one category of RA, and the pathogenic macrophage populations tend to exist in a different category. Because of this, we can start asking questions about how these specific partners work together.”

Source: University of Colorado Anschutz Medical Campus

Categories : AgeingTags :

Immunomodulator Keeps Subclinical Arthritis from Developing into Full-blown Form

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In a 12-month trial involving patients with “preclinical” rheumatoid arthritis, treatment with the immunomodulator abatacept (Orencia) kept the condition from becoming clinical, according to findings presented at the European Alliance of Associations for Rheumatology (EULAR) annual meeting.

Rheumatologists have long sought to nip rheumatoid arthritis (RA) in the bud, with many studies supporting early aggressive treatment on RA diagnosis. This has never been recommended for biologic therapies however.

Nevertheless, some patients show up at arthritis clinics with a few painful joints and other features such as RA-related serum biomarkers that suggest progression to full-blown RA is likely. Would aggressive treatment help slow their decline into RA?

In a phase IIb randomised trial involving patients in the UK and Netherlands who were at high risk for developing RA, only seven of the 110 assigned to abatacept had gone on to develop clinical arthritis after 1 year, compared with 30 of 103 in a placebo group.

The effect waned after abatacept was stopped at the one-year mark, and in the following year, 20 more patients in the abatacept group developed clinical arthritis, as did another eight in the placebo group.

Though the abatacept regimen held the edge for a full two years, projections showed that it was likely that the abatacept group would catch up with additional follow-up. At the same time, abatacept had no particular safety issues and thus could likely be continued.

A decade ago, Andrew Cope, MD, MBBS, of King’s College London colleagues thought about aggressive prevention, registering the current trial, Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA), in 2014. In a 2019 description of the protocol, they explained the selection of abatacept because “it targets immune reactions early in the chain of events leading to inflammation in RA. It functions by interrupting the interaction between T cells and antigen-presenting cells, attenuating the co-stimulatory signals required for T-cell activation, differentiation and effector responses,” thereby resulting “in downstream immunomodulatory effects on other inflammatory cells of the immune system.”

Participants had to show joint pain but no synovitis, plus either test positive for anti-citrullinated protein antigen (ACPA) antibodies and for rheumatoid factor (RF), or show high levels of ACPA antibodies without RF. The primary endpoint was development of clinically apparent arthritis in at least three joints or diagnosis of RA according to standard criteria.

While the preventive effect seen in the primary analysis did not hold up across the whole sample, Cope noted that it appeared more so in one very-high-risk subgroup: 49 patients who had some level of IgG ACPA antibodies and who were also positive for a series of other biomarkers, including RF, IgA ACPA antibodies, anti-carbamylated protein antibodies, and anti-acetylated peptide antibodies. For this subgroup, only about 10% of those who had taken abatacept progressed to clinical arthritis after two years, versus 50% of those assigned to placebo.

Source: MedPage Today

Categories : Diseases, Syndromes and Conditions Immune SystemTags :

Autoimmune Disorders Now Affect Roughly One in Ten Individuals

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A population-based study of 22 million people in the UK estimates that around one in ten individuals in the UK now live with an autoimmune disorder. The findings, published in The Lancet, also highlight important socioeconomic, seasonal and regional differences for several autoimmune disorders, providing new clues as to what factors may be involved in these conditions.

There are more than 80 known autoimmune diseases, including conditions like rheumatoid arthritis, type 1 diabetes and multiple sclerosis, some of which have been increasing in the last few decades.

This has raised the question whether overall incidence of autoimmune disorders is on the rise and what factors are involved, such as environmental factors or behavioural changes in society. The exact causes of autoimmune diseases remain largely unknown, including how much can be attributed to a genetic predisposition to disease and how much is down to exposure to environmental factors.

The study used anonymised electronic health data from 22 million individuals in the UK to investigate 19 of the most common autoimmune diseases. The authors examined whether incidence of autoimmune diseases is rising over time, who is most affected by these conditions and how different autoimmune diseases may co-exist with each other.

They found that the 19 autoimmune diseases studied affect around 10% of the population. This is higher than previous estimates, which ranged from 3–9% and often relied on smaller sample sizes and included fewer autoimmune conditions. The analysis also highlighted a higher incidence in women (13%) than men (7%).

The research discovered evidence of socioeconomic, seasonal and regional disparities for several autoimmune disorders, suggesting that these conditions are unlikely to be caused by genetic differences alone. This observation may point to the involvement of potentially modifiable risk factors such as smoking, obesity or stress. It was also found that in some cases a person with one autoimmune disease is more likely to develop a second, compared to someone without an autoimmune disease.

Dr Nathalie Conrad at the University of Oxford said: “We observed that some autoimmune diseases tended to co-occur with one another more commonly than would be expected by chance or increased surveillance alone. This could mean that some autoimmune diseases share common risk factors, such as genetic predispositions or environmental triggers. This was particularly visible among rheumatic diseases and among endocrine diseases. But this phenomenon was not generalised across all autoimmune diseases. Multiple sclerosis, for example, stood out as having low rates of co-occurrence with other autoimmune diseases, suggesting a distinct pathophysiology.”

These findings reveal novel patterns that will inform the design of further research into the possible common causes of different autoimmune diseases.

Professor Geraldine Cambridge at UCL Medicine said: “Our study highlights the considerable burden that autoimmune diseases place upon individuals and the wider population. Disentangling the commonalities and differences within this large and varied set of conditions is a complex task. There is a crucial need, therefore, to increase research efforts aimed at understanding the underlying causes of these conditions, which will support the development of targeted interventions to reduce the contribution of environmental and social risk factors.”

Source: University College London

Categories : Diseases, Syndromes and Conditions Environmental EffectsTags :

Strong Link Between Polycyclic Aromatic Hydrocarbons and Rheumatoid Arthritis Risk

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Exposure to polycyclic aromatic hydrocarbons (PAH), formed from burning various substances such as coal, wood or tobacco, or from grilled meat, is strongly linked to a person’s risk of developing rheumatoid arthritis, suggests research published in the open access journal BMJ Open.

These chemicals also seem to account for most of smoking’s impact on risk of the disease, the findings indicate. Growing evidence links several environmental toxicants with various long term conditions. But few studies have looked at their association with inflammatory conditions, such as rheumatoid arthritis, which is thought to arise from an interplay between genes, sex, and age, and environmental factors, including smoking, nutrition, and lifestyle.

To try and shed some light on the potential role of environmental exposure on rheumatoid arthritis risk, the researchers drew on responses to the nationally representative US National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016.

NHANES evaluates a wide variety of toxicants, including PAH; chemicals used in the manufacture of plastics and various consumer products (PHTHTEs); and volatile organic compounds (VOCs), derived from paints, cleaning agents, and pesticides, among other things; along with data related to health, nutrition, behaviours and the environment.

The study included 21 987 adults, 1418 of whom had rheumatoid arthritis and 20 569 of whom didn’t. Blood and urine samples were taken to measure the total amount of PAH (7090 participants), PHTHTEs (7024), and VOCs (7129) in the body.

The odds of rheumatoid arthritis were highest among those in the top 25% of bodily PAH levels, irrespective of whether or not they were former or current smokers.

After accounting for potentially influential factors, including dietary fibre intake, physical activity, smoking, household income, educational attainment, age, sex, and weight (BMI), only one PAH, 1-hydroxynaphthalene, was strongly associated with higher odds (80%) of the disease.

PHTHTE and VOC metabolites weren’t associated with heightened risk after accounting for potentially influential factors.

Somewhat surprisingly, however, smoking wasn’t associated with heightened rheumatoid arthritis risk either, after accounting for PAH levels in the body. 

And further analysis to separate out the influences of PAH and smoking showed that bodily PAH level accounted for 90% of the total effect of smoking on rheumatoid arthritis risk.

This is an observational study, and as such, can’t determine cause. And the researchers acknowledge various limitations to their findings, including that measurements of environmental toxicants in fat (adipose) tissue weren’t available.

Nor did they measure heavy metal levels which have previously been linked to rheumatoid arthritis risk. Cigarettes are a major source of the heavy metal cadmium.

But they write: “To our knowledge, this is the first study to demonstrate that PAH not only underlie the majority of the relationship between smoking and [rheumatoid arthritis], but also independently contribute to [it]. 

“This is important as PAH are ubiquitous in the environment, derived from various sources, and are mechanistically linked by the aryl hydrocarbon receptor to the underlying pathophysiology of [rheumatoid arthritis].”

They add: “While PAH levels tend to be higher in adults who smoke…other sources of PAH exposure include indoor environments, motor vehicle exhaust, natural gas, smoke from wood or coal burning fires, fumes from asphalt roads, and consuming grilled or charred foods.

“This is pertinent as households of lower socioeconomic status generally experience poorer indoor air quality and may reside in urban areas next to major roadways or in high traffic areas.” These people may therefore be particularly vulnerable, they suggest.

Source: The BMJ

Categories : COVID Diseases, Syndromes and ConditionsTags :

Prior COVID Infection Linked to New Autoimmune Conditions

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In a new entry to the growing list of lasting complications from COVID infection, a large German cohort study of over 600 000 COVID patients indicates that new autoimmune conditions may result from previous COVID infection. The findings, which are awaiting peer review on the MedRxiv preprint server, show that the odds of new autoimmune conditions appear to increase in line with the severity of COVID infection.

After the acute phase of infection, some people may develop long-lasting symptoms, known as post-COVID, which are consistent with COVID infection and last more than 12 weeks. Most studies to date have focused on symptoms that partly wane over time. Many studies examined a small selective sample of patients, and only a few studies included a control group or information on chronic health conditions, such as SARS-CoV-2 infection.

Compared to post-COVID emergence of cardiovascular and other diseases, autoimmune diseases are less discussed in the literature, although autoantibodies could be found in patients after SARS-CoV-2 infection. So far there is limited evidence on newly manifested autoimmune diseases after an infection based on several case reports and one recent cohort study using UK health record data. In addition, COVID itself has some similarities with systemic autoimmune rheumatic diseases, which could make diagnosis difficult.

The researchers selected a cohort from German routine health care data, identifying individuals with polymerase chain reaction (PCR)-confirmed COVID through December 31, 2020. Patients were matched 1:3 to control patients without COVID. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyse the onset of autoimmune diseases during the post-acute period. The researchers calculated the incidence rates (IR) per 1000 person-years for each outcome and patient group, and estimated incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding COVID.

In total, 641 704 patients with COVID were included. When comparing the incidence rates in the COVID and matched control groups, the researchers found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune disease of the vasculitis group. Patients with a more severe course of COVID were at a greater risk for incident autoimmune diseases. These risk increases were as follows:

  • 41% higher risk of Grave’s disease
  • 42–45% higher risk of rheumatoid arthritis
  • 25% higher risk of type 1 diabetes
  • 27-29% higher risk of Crohn’s disease

The researchers concluded that SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection.

Categories : Environmental EffectsTags :

Occupational Dust and Fumes Exposure may Raise Rheumatoid Arthritis Risk

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Breathing in common workplace dust and fumes may increase the risk of developing severe rheumatoid arthritis, especially in combination with smoking and genetic susceptibility to the disease, suggests a new study published in The Annals of the Rheumatic Diseases.

Rheumatoid arthritis (RA) is a chronic autoimmune joint disorder affecting up to 1% of the population. The presence of so-called anti-citrullinated protein antibodies (ACPA) denotes a worse prognosis with higher rates of erosive joint damage.

Cigarette smoking is already known as a risk factor for developing RA, but the impact of breathing in workplace dust and fumes, such as vapours, gases, and solvents, remains unclear.

Increased risk of ACPA-positive rheumatoid arthritis

Researchers at Karolinska Institutet drew on data from the Swedish case-control study EIRA (Epidemiological Investigation of RA), comprising 4033 people diagnosed with RA between 1996 and 2017 and 6485 randomly selected healthy controls matched for age and sex. Personal job histories were used to estimate the exposure to 32 inhalable workplace agents. Each participant was assigned a genetic risk score based on their genetic susceptibility to developing RA.

Individuals who had been exposed to any of the occupational agents had a 25 per cent higher risk of developing ACPA-positive RA, and the risk increased with a longer duration of exposure or with more types of exposed agents. 17 out of 32 agents, including quartz, asbestos, diesel fumes, gasoline fumes, carbon monoxide, and fungicides, were strongly associated with an increased risk of developing ACPA-positive RA, but only a few agents were associated with ACPA-negative RA.

Interaction with smoking and risk genes

Individuals who were exposed to smoking as well as inhalable workplace agents, in combination with having a high genetic risk score, had an 18 times higher risk of developing ACPA-positive RA compared with those who were not exposed to any of these three factors.

“Occupational inhalable agents could act as important environmental triggers in RA development and interact with smoking and RA risk genes,” says Karolinska Institutet professor and corresponding author Lars Klareskog. “Preventive strategies aimed at reducing occupational hazards and smoking are warranted for reduction of the burden of RA, especially for those who are genetically vulnerable.”

Because it is an observational study, it cannot establish any causal relationships.

Source: Karolinska Institutet

Categories : AgeingTags :

Assessing the Effectiveness of Chinese Traditional Medicine for Rheumatoid Arthritis

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Chinese traditional medicine based on combinations of typically 5 to ten plants, usually boiled and administered as a decoction or tea, has long been used to treat rheumatoid arthritis (RA), but few clinical trials have tested its potential. A review in the Journal of Internal Medicine outlines a strategy to analyse the ability of different mixtures of plants used in Chinese medicine to combat RA.

One fundamental of traditional medicine is to prevent disease. RA is an autoimmune, inflammatory and chronic disease that primarily affects the joints of 0.5%–1% of the population. In two out of three of the cases, the patients are characterised by the presence of autoantibodies such as the rheumatoid factor and the more disease-specific autoantibody against citrullinated proteins, so-called ‘ACPA’ (anticitrullinated protein/peptide antibodies). ACPA positivity is also strongly associated with specific variations in the HLA-DRB1 gene, the shared epitope alleles. Together with smoking, these factors account for the major risks of developing RA. 

The researchers’ 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 RA.

“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.”

Source: Wiley

Categories : AgeingTags : 1 Comment

Treatment of Rheumatoid Arthritis Before Disease Develops Yields Benefits

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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

Categories : Diseases, Syndromes and ConditionsTags :

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