BACKGROUND: The presence of ACPA significantly increases the risk of developing RA. Dysregulation of lymphocyte subpopulations was previously described in RA. Our objective was to propose the predictive model for progression to clinical arthritis based on peripheral lymphocyte subsets and ACPA in individuals who are at risk of RA. METHODS: Our study included 207 at-risk individuals defined by the presence of arthralgias and either additional ACPA positivity or meeting the EULAR definition for clinically suspect arthralgia. For the construction of predictive models, 153 individuals with symptom duration ≥12 months who have not yet progressed to arthritis were included. The lymphocyte subsets were evaluated using flow cytometry and anti-CCP using ELISA. RESULTS: Out of all individuals with arthralgia, 41 progressed to arthritis. A logistic regression model with baseline peripheral blood lymphocyte subpopulations and ACPA as predictors was constructed. The resulting predictive model showed that high anti-CCP IgG, higher percentage of CD4+ T cells, and lower percentage of T and NK cells increased the probability of arthritis development. Moreover, the proposed classification decision tree showed that individuals having both high anti-CCP IgG and low NK cells have the highest risk of developing arthritis. CONCLUSIONS: We propose a predictive model based on baseline levels of lymphocyte subpopulations and ACPA to identify individuals with arthralgia with the highest risk of progression to clinical arthritis. The final model includes T cells and NK cells, which are involved in the pathogenesis of RA. This preliminary model requires further validation in larger at-risk cohorts.

• MeSH
• artralgie * imunologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• podskupiny lymfocytů * imunologie   MeSH
• prediktivní hodnota testů MeSH
• progrese nemoci * MeSH
• protilátky proti citrulinovaným peptidům * krev   imunologie   MeSH
• revmatoidní artritida * imunologie   krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• artritida diagnóza   etiologie   imunologie   klasifikace   mikrobiologie   MeSH
• myozitida diagnóza   etiologie   klasifikace   MeSH
• osteoartróza diagnóza   farmakoterapie   klasifikace   MeSH
• revmatoidní artritida diagnostické zobrazování   diagnóza   farmakoterapie   MeSH
• revmatologie * klasifikace   MeSH
• spondylartritida diagnóza   etiologie   klasifikace   MeSH
• systémový lupus erythematodes diagnóza   klasifikace   komplikace   MeSH
• vaskulitida diagnóza   etiologie   klasifikace   MeSH
• Publikační typ
• přehledy MeSH

This commentary explores the potential cardiovascular (CV) benefits of combining methotrexate (MTX) and Janus kinase inhibitors (JAKis) in the treatment of rheumatoid arthritis (RA). While European guidelines recommend MTX as first-line treatment, concerns about the CV risks associated with JAKis have emerged. This article reviews the existing literature to assess the role of concomitant MTX in reducing CV risk when used with JAKis. Clinical trials confirm the efficacy of JAKis in combination with MTX in terms of treatment outcomes in RA. However, the number of major adverse cardiovascular events (MACEs) reported is too low to draw conclusions on adverse CV outcomes. Indirect evidence does, however, suggest potential protective effects of MTX on CV outcomes, as several mechanisms may contribute to MTX's cardioprotective effects, including reduced inflammation, adenosine monophosphate-activated protein kinase (AMPK) activation, increased cholesterol efflux, and adenosine accumulation. These mechanisms and the available data may support the case for CV benefits of concomitant MTX when JAKis are used in the treatment of patients with RA, although further research is needed. In particular, the lipid paradox associated with RA highlights the complex relationship between RA treatments (MTX, JAKis, tumor necrosis factor (TNF) inhibitors, and interleukin (IL)-6 receptor inhibitors), inflammation, different lipid profiles, and CV risk. In the absence of contraindications and when MTX is tolerated, this commentary suggests the concomitant use of MTX and JAKis as a preferred option for optimizing CV protection in patients with RA.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Individuals with anti-citrullinated protein antibodies (ACPAs) and subclinical inflammatory changes in joints are at high risk of developing rheumatoid arthritis. Treatment strategies to intercept this pre-stage clinical disease remain to be developed. We aimed to assess whether 6-month treatment with abatacept improves inflammation in preclinical rheumatoid arthritis. METHODS: The abatacept reversing subclinical inflammation as measured by MRI in ACPA positive arthralgia (ARIAA) study is a randomised, international, multicentre, double-blind, placebo-controlled trial done in 14 hospitals and community centres across Europe (11 in Germany, two in Spain, and one in the Czech Republic). Adults (aged ≥18 years) with ACPA positivity, joint pain (but no swelling), and signs of osteitis, synovitis, or tenosynovitis in hand MRI were randomly assigned (1:1) to weekly subcutaneous abatacept 125 mg or placebo for 6 months followed by a double-blind, drug-free, observation phase for 12 months. The primary outcome was the proportion of participants with any reduction in inflammatory MRI lesions at 6 months. The primary efficacy analysis was done in the modified intention-to-treat population, which included participants who were randomly assigned and received study medication. Safety analyses were conducted in participants who received the study medication and had at least one post-baseline observation. The study was registered with the EUDRA-CT (2014-000555-93). FINDINGS: Between Nov 6, 2014, and June 15, 2021, 139 participants were screened. Of 100 participants, 50 were randomly assigned to abatacept 125 mg and 50 to placebo. Two participants (one from each group) were excluded due to administration failure or refusing treatment; thus, 98 were included in the modified intention-to-treat population. 70 (71%) of 98 participants were female and 28 (29%) of 98 were male. At 6 months, 28 (57%) of 49 participants in the abatacept group and 15 (31%) of 49 participants in the placebo group showed improvement in MRI subclinical inflammation (absolute difference 26·5%, 95% CI 5·9-45·6; p=0·014). Four (8%) of 49 participants in the abatacept group and 17 (35%) of 49 participants in the placebo group developed rheumatoid arthritis (hazard ratio [HR] 0·14 [0·04-0·47]; p=0·0016). Improvement of MRI inflammation (25 [51%] of 49 participants in the abatacept group, 12 [24%] of 49 in the placebo group; p=0·012) and progression to rheumatoid arthritis (17 [35%] of 49, 28 [57%] of 49; HR 0·14 [0·04-0·47]; p=0·018) remained significantly different between the two groups after 18 months, 12 months after the end of the intervention. There were 12 serious adverse events in 11 participants (four [8%] of 48 in the abatacept group and 7 [14%] of 49 in the placebo group). No deaths occurred during the study. INTERPRETATION: 6-month treatment with abatacept decreases MRI inflammation, clinical symptoms, and risk of rheumatoid arthritis development in participants at high risk. The effects of the intervention persist through a 1-year drug-free observation phase. FUNDING: Innovative Medicine Initiative.

• MeSH
• abatacept škodlivé účinky   MeSH
• antirevmatika * škodlivé účinky   MeSH
• artralgie chemicky indukované   MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• revmatoidní artritida * diagnostické zobrazování   farmakoterapie   MeSH
• výsledek terapie MeSH
• zánět farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

There is increasing knowledge in the recognition of individuals at risk for progression to rheumatoid arthritis (RA) before the clinical manifestation of the disease. This prodromal phase preceding the manifestation of RA may represent a "window of opportunity" for preventive interventions that may transform the clinical approach to this disease. However, limited evidence exists in support of effective interventions to delay the onset or even halt the manifestation of RA. Given the multifactorial nature of RA development and disease progression, the latest guidelines for established RA stress the use of integrative interventions and multidisciplinary care strategies, combining pharmacologic treatment with non-pharmacological approaches. Accordingly, individuals at risk of RA could be offered an integrative, multifactorial intervention approach. Current data point toward pharmacological intervention reverting the subclinical inflammation and delay in the disease onset. In addition, targeting life style modifiable factors (smoking cessation, dental health, physical activity, and diet) may presumably improve RA prognosis in individuals at risk, mainly by changes in epigenetics, autoantibodies, cytokines profiles, and microbiome. Nonetheless, the benefits of multidisciplinary interventions to halt the manifestation of RA in at-risk individuals remain unknown. As there is a growing knowledge of possible pharmacological intervention in the preclinical phase, this narrative review aims to provide a comprehensive overview of non-pharmacological treatments in individuals at risk of RA. Considering the mechanisms preceding the clinical manifestation of RA we explored all aspects that would be worth modifying and that would represent an integrative non-pharmacological care for individuals at risk of RA.

• MeSH
• autoprotilátky MeSH
• lidé MeSH
• prognóza MeSH
• revmatoidní artritida * terapie   farmakoterapie   MeSH
• zánět MeSH
• životní styl MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Revmatologie zažívá v posledních letech významný pokrok, který je důsledkem zdůrazňování časné diagnostiky a uplatňo- vání principů léčby k cíli, stejně jako nových imunopatogenetických poznatků a dostupnosti širokého spektra biologických a cílených syntetických léčivých přípravků. V tomto sdělení přinášíme nové poznatky z oblasti diagnostiky a léčby vybraných revmatických onemocnění, a to konkrétně revmatoidní artritidy, spondyloartritid, systémového lupus erythematodes, systémové sklerodermie, idiopatických zánětlivých myopatií, systémových vaskulitid, revmatické polymyalgie a obrov- skobuněčné arteriiitidy a také osteoartrózy. Toto sdělení si klade za cíl přinést souhrn nejnovějších poznatků a trendů v diagnostice a léčbě těchto revmatických onemocnění, které mají zásadní vliv na kvalitu života pacientů.

Rheumatology has experienced significant advances in recent years as a result of the emphasis on early diagnosis and the application of treat-to-target principles, as well as new immunopathogenetic findings and the availability of a wide range of biologic and targeted synthetic drugs. In this communication, we present new findings in the diagnosis and treatment of selected rheumatic diseases, specifically rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, systemic scleroderma, idiopathic inflammatory myopathies, systemic vasculitis, rheumatic polymyalgia and giant cell arteritis, and osteoarthritis. This communication aims to provide a summary of the latest findings and trends in the diagnosis and treatment of these rheumatic diseases, which have a major impact on the quality of life of patients.

• MeSH
• ANCA-asociované vaskulitidy diagnóza   farmakoterapie   MeSH
• antirevmatika aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• axiální spondyloartritida diagnóza   farmakoterapie   komplikace   MeSH
• biologická terapie metody   MeSH
• imunoterapie adoptivní metody   MeSH
• inhibitory Janus kinas aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• intravenózní imunoglobuliny aplikace a dávkování   terapeutické užití   MeSH
• methotrexát aplikace a dávkování   terapeutické užití   MeSH
• monoklonální protilátky aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• myozitida diagnóza   farmakoterapie   imunologie   MeSH
• obrovskobuněčná arteritida diagnóza   farmakoterapie   MeSH
• osteoartróza diagnóza   farmakoterapie   MeSH
• polymyalgia rheumatica diagnóza   terapie   MeSH
• psoriatická artritida diagnóza   farmakoterapie   komplikace   MeSH
• revmatické nemoci * diagnóza   farmakoterapie   komplikace   MeSH
• revmatoidní artritida diagnóza   farmakoterapie   komplikace   MeSH
• rizikové faktory MeSH
• systémová sklerodermie diagnóza   farmakoterapie   komplikace   MeSH
• systémový lupus erythematodes diagnóza   farmakoterapie   komplikace   MeSH

In this article, we review published literature on "telerheumatology", a term describing the use of telemedicine in rheumatology. This field has received considerable recent attention through the development of efficient digital technologies, resulting in a good level of satisfaction among patients and health care professionals. In 2020, the social distancing constraints during the COVID-19 pandemic accelerated more widespread adoption worldwide. Telerheumatology is particularly suited for patients with rheumatoid arthritis who have achieved a sustained therapeutic target of remission or low disease activity. To facilitate remote consultations and meet expectations of rheumatologists and patients, international and national guidelines have recently been proposed and existing tools, such as Patient-Reported Outcomes questionnaires, have had to be digitally adapted. In addition, telerheumatology toolkits are proposed by the Arab League of Associations for Rheumatology (ArLAR), the Association of American Medical College (AAMC), and the American College of Rheumatology (ACR) for all learners, from medical students to practicing clinicians, encouraging the acquisition of telehealth skills and facilitating their integration into their routine clinical practice. The main benefits reported for this mode of health care are greater access to specialty care, flexibility, reduced rates of missed appointments, as well as improved patient engagement and autonomy. Limitations include the absence of physical examination. However, to implement telerheumatology effectively and widely in daily clinical practice, some barriers still need to be addressed. These include training of health care professionals, technological restrictions and reimbursement mechanisms. Despite the advantages of telerheumatology, it is not intended to replace face-to-face visits, but rather as a way to enhance access to care, service delivery and health care support for patients.

• MeSH
• konzultace na dálku * metody   MeSH
• lidé MeSH
• pandemie MeSH
• poskytování zdravotní péče MeSH
• revmatologie * metody   MeSH
• telemedicína * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

MicroRNAs (miRNAs) are small non-coding single-stranded RNAs of about 22 nucleotides in length that act as post-transcriptional regulators of gene expression. Depending on the complementarity between miRNA and target mRNA, cleavage, destabilization, or translational suppression of mRNA occurs within the RISC (RNA-induced silencing complex). As gene expression regulators, miRNAs are involved in a variety of biological functions. Dysregulation of miRNAs and their target genes contribute to the pathophysiology of many diseases, including autoimmune and inflammatory disorders. MiRNAs are also present extracellularly in their stable form in body fluids. Their incorporation into membrane vesicles or protein complexes with Ago2, HDL, or nucleophosmin 1 protects them against RNases. Cell-free miRNAs can be delivered to another cell in vitro and maintain their functional potential. Therefore, miRNAs can be considered mediators of intercellular communication. The remarkable stability of cell-free miRNAs and their accessibility in body fluid makes them potential diagnostic or prognostic biomarkers and potential therapeutic targets. Here we provide an overview of the potential role of circulating miRNAs as biomarkers of disease activity, therapeutic response, or diagnosis in rheumatic diseases. Many circulating miRNAs reflect their involvement in the pathogenesis, while for plenty, their pathogenetic mechanisms remain to be explored. Several miRNAs described as biomarkers were also shown to be of therapeutic potential, and some miRNAs are already tested in clinical trials.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH