AIMS: To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP). METHODS AND RESULTS: The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014-19. The treatment goal for BP was <140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid-lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high risk groups, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two per cent had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three-drug combination. CONCLUSION: We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.

• Klíčová slova
• Audit, Blood pressure, Lipids, Prevention, Rheumatoid arthritis, Statins,
• MeSH
• dyslipidemie * diagnóza   farmakoterapie   epidemiologie   MeSH
• hypertenze * diagnóza   farmakoterapie   epidemiologie   MeSH
• kardiovaskulární nemoci * diagnóza   epidemiologie   prevence a kontrola   MeSH
• lidé MeSH
• lipidy MeSH
• revmatoidní artritida * diagnóza   farmakoterapie   epidemiologie   MeSH
• rizikové faktory MeSH
• statiny * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lipidy MeSH
• statiny * MeSH

The study aimed to compare treatment retention for first-line TNF inhibitor (TNFi) in the ATTRA registry patients receiving either combination with conventional synthetic DMARDs or TNFi as monotherapy. A retrospective multicenter study analyzed data of all adult patients with rheumatoid arthritis (n = 3032) starting TNF inhibitor as the first-line biological therapy in combination with csDMARDs or in monotherapy from January 1st 2012 to December 31st 2020. Kaplan-Meier method was employed to calculate drug retentions. Survival curves of treatment retentions were compared through Log-rank test between the studied subgroups. The hazard ratio for drug discontinuation was assessed through univariate cox regression models. In patients who started the first line TNFi therapy, the median treatment retention was 47.7 (42.2; 53.1) months for combination therapy and 22.7 (14.9; 30.6) months for TNFi monotherapy (p < 0.001). Estimated one-year survival was higher in patients on TNFi combined with csDMARDs as compared with TNFi monotherapy (75.3% vs 65.7%); two-year survival rate was 63.2% vs 49.2%, three-year survival rate was 55.4% vs 42.4% and five-year survival 44.9% vs 26.4% of patients. The estimated survival on the first TNFi was higher in patients taking combination therapy with methotrexate than with other csDMARDs (p = 0.003). Use of csDMARDs co-medication was associated with significantly better first TNFi drug survival compared to monotherapy. The combination of TNFi with MTX is more effective than the combination with leflunomide, which did not demonstrate a significant effect.

• Klíčová slova
• Drug persistence, Methotrexate, Registry, Rheumatoid arthritis, TNF inhibitor, csDMARDs,
• MeSH
• antirevmatika * škodlivé účinky   MeSH
• dospělí MeSH
• inhibitory TNF terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• methotrexát škodlivé účinky   MeSH
• registrace MeSH
• retrospektivní studie MeSH
• revmatoidní artritida * chemicky indukované   diagnóza   farmakoterapie   MeSH
• TNF-alfa terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antirevmatika * MeSH
• inhibitory TNF MeSH
• methotrexát MeSH
• TNF-alfa MeSH

OBJECTIVE: To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA). METHODS: An EULAR Task Force was established comprising 34 individuals: 26 rheumatologists, patient partners and rheumatology experienced health professionals. Two systematic literature reviews addressed clinical questions around diagnostic challenges, and pharmacological and non-pharmacological therapeutic strategies in D2T RA. PtCs were formulated based on the identified evidence and expert opinion. Strength of recommendations (SoR, scale A-D: A typically consistent level 1 studies and D level 5 evidence or inconsistent studies) and level of agreement (LoA, scale 0-10: 0 completely disagree and 10 completely agree) of the PtCs were determined by the Task Force members. RESULTS: Two overarching principles and 11 PtCs were defined concerning diagnostic confirmation of RA, evaluation of inflammatory disease activity, pharmacological and non-pharmacological interventions, treatment adherence, functional disability, pain, fatigue, goal setting and self-efficacy and the impact of comorbidities. The SoR varied from level C to level D. The mean LoA with the overarching principles and PtCs was generally high (8.4-9.6). CONCLUSIONS: These PtCs for D2T RA can serve as a clinical roadmap to support healthcare professionals and patients to deliver holistic management and more personalised pharmacological and non-pharmacological therapeutic strategies. High-quality evidence was scarce. A research agenda was created to guide future research.

• Klíčová slova
• arthritis, fibromyalgia, inflammation, rheumatoid, ultrasonography,
• MeSH
• adherence k farmakoterapii MeSH
• antirevmatika aplikace a dávkování   terapeutické užití   MeSH
• cvičení MeSH
• hepatitida B komplikace   farmakoterapie   MeSH
• hepatitida C komplikace   farmakoterapie   MeSH
• kognitivně behaviorální terapie MeSH
• komorbidita MeSH
• lidé MeSH
• revmatoidní artritida komplikace   diagnóza   farmakoterapie   terapie   MeSH
• určení symptomu MeSH
• vzdělávání pacientů jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• směrnice pro lékařskou praxi MeSH
• Názvy látek
• antirevmatika MeSH

Production of particles and their adaptation in the pharmacology became an object of interest, and they are the currently introduced therapies based on the use of micro and nanoparticles. The use of gold particles is not an exception. This review has focused on the application of gold micro and nanoparticles in pharmacology and biomedicine. The particles can be used for diagnosis respective theranostic of cancer, rheumatoid arthritis and as antimicrobial means. Besides these applications, specifications of gold, gold particles, and colloidal gold manufacturing and their comparison with the solid gold, are described as well. This review is based on a survey of actual scientific literature.

• Klíčová slova
• Biomedicine, cancer, chrysotherapy, drug delivery, gold, hyperthermia, magnetic resonance imaging, microparticles, nanomedicine, nanoparticles, nanotechnology, photothermal therapy, theragnostic.,
• MeSH
• antiflogistika chemie   farmakologie   MeSH
• antiinfekční látky chemie   farmakologie   MeSH
• antitumorózní látky chemie   farmakologie   MeSH
• Bacteria účinky léků   MeSH
• biomedicínský výzkum MeSH
• houby účinky léků   MeSH
• lidé MeSH
• nádory diagnóza   farmakoterapie   MeSH
• nanočástice chemie   MeSH
• revmatoidní artritida diagnóza   farmakoterapie   MeSH
• zlato chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antiflogistika MeSH
• antiinfekční látky MeSH
• antitumorózní látky MeSH
• zlato MeSH

Rheumatoid arthritis (RA) is a chronic autoimmune disease considered as a multistep process spanning from the interaction of genetic (e.g., shared epitope or non-HLA loci), environmental and behavioral risk factors (e.g., smoking) leading to breaking immune tolerance and autoimmune processes such as the production of autoantibodies (e.g., antibodies against citrullinated proteins ACPA or rheumatoid factors, RF), development of the first symptoms without clinical arthritis, and, finally, the manifestation of arthritis. Despite the typical joint involvement in established RA, the pathogenesis of the disease likely begins far from joint structures: in the lungs or periodontium in association with citrullination, intestinal microbiome, or adipose tissue, which supports normal findings in synovial tissue in ACPA+ patients with arthralgia. The presence of ACPA is detectable even years before the first manifestation of RA. The pre-clinical phase of RA is the period preceding clinically apparent RA with ACPA contributing to the symptoms without subclinical inflammation. While the combination of ACPA and RF increases the risk of progression to RA by up to 10 times, increasing numbers of novel autoantibodies are to be investigated to contribute to the increased risk and pathogenesis of RA. With growing knowledge about the course of RA, new aspiration emerges to cure and even prevent RA, shifting the "window of opportunity" to the pre-clinical phases of RA. The clinical definition of individuals at risk of developing RA (clinically suspect arthralgia, CSA) makes it possible to unify these at-risk individuals' clinical characteristics for "preventive" treatment in ongoing clinical trials using mostly biological or conventional synthetic disease-modifying drugs. However, the combination of symptoms, laboratory, and imaging biomarkers may be the best approach to select the correct target at-risk population. The current review aims to explore different phases of RA and discuss the potential of (non)pharmacological intervention aiming to prevent RA.

• Klíčová slova
• ACPA, Clinically suspect arthralgia, Imaging, Pre-RA, Symptoms, Treatment,
• MeSH
• artralgie MeSH
• autoprotilátky MeSH
• lidé MeSH
• revmatoidní artritida * diagnóza   prevence a kontrola   MeSH
• revmatoidní faktor MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• autoprotilátky MeSH
• revmatoidní faktor MeSH

OBJECTIVES: Individuals carrying antibodies against citrullinated proteins (ACPA) are at high risk of developing RA. EULAR provided a clinical definition of individuals with arthralgia suspicious for progression to RA (clinically suspect arthralgia, CSA). The alteration of monocyte subpopulations in patients with established RA has been previously described. We analysed peripheral blood monocyte subpopulations in individuals with arthralgia at risk of RA. METHODS: We included 70 at-risk individuals, defined as having arthralgia without arthritis and being either ACPA+ or meeting the clinical CSA definition, 23 patients with early RA (ERA) and 19 healthy controls (HCs). Monocytes classified as classical (CD14++CD16-), intermediate (CD14++CD16+/++) and nonclassical (CD14-/+CD16++) were analysed by flow cytometry. RESULTS: Of the 70 at-risk individuals, 46 were ACPA+ and 45 met the CSA definition. The at-risk individuals and, especially, ERA patients had a lower percentage of classical monocytes and a higher percentage of nonclassical monocytes than the HCs. ACPA positivity had no effect on the difference in the distribution of the monocyte subsets between at-risk individuals and ERA patients, but a difference was determined in those reaching the ERA phase. However, when compared with HCs, the shift of monocyte subsets was more significant in ACPA+ than in ACPA- individuals with arthralgia. This trend was observed in individuals who did not meet the CSA definition. This finding was, however, determined by a selection bias, as these individuals were solely ACPA+. CONCLUSION: The shift from classical to nonclassical monocyte subpopulations was observed already in individuals at risk of developing RA.

• Klíčová slova
• ACPA, arthralgia, monocytes, pre-RA, rheumatoid arthritis,
• MeSH
• artralgie etiologie   MeSH
• C-reaktivní protein analýza   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• monocyty metabolismus   MeSH
• následné studie MeSH
• progrese nemoci MeSH
• protilátky proti citrulinovaným peptidům krev   MeSH
• revmatoidní artritida krev   diagnóza   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• C-reaktivní protein MeSH
• protilátky proti citrulinovaným peptidům MeSH

OBJECTIVES: RF and ACPA are used as diagnostic tools and their presence has been associated with clinical response to some biologic DMARDs (bDMARDs) in RA. This study compared the impact of seropositivity on drug discontinuation and effectiveness of bDMARDs in patients with RA, using head-to-head comparisons in a real-world setting. METHODS: We conducted a pooled analysis of 16 observational RA registries. Inclusion criteria were a diagnosis of RA, initiation of treatment with rituximab (RTX), abatacept (ABA), tocilizumab (TCZ) or TNF inhibitors (TNFis) and available information on RF and/or ACPA status. Drug discontinuation was analysed using Cox regression, including drug, seropositivity, their interaction, adjusting for concomitant and past treatments and patient and disease characteristics and accounting for country and calendar year of bDMARD initiation. Effectiveness was analysed using the Clinical Disease Activity Index evolution over time. RESULTS: Among the 27 583 eligible patients, the association of seropositivity with drug discontinuation differed across bDMARDs (P for interaction <0.001). The adjusted hazard ratios for seropositive compared with seronegative patients were 1.01 (95% CI 0.95, 1.07) for TNFis, 0.89 (0.78, 1.02)] for TCZ, 0.80 (0.72, 0.88) for ABA and 0.70 (0.59, 0.84) for RTX. Adjusted differences in remission and low disease activity rates between seropositive and seronegative patients followed the same pattern, with no difference in TNFis, a small difference in TCZ, a larger difference in ABA and the largest difference in RTX (Lundex remission difference +5.9%, low disease activity difference +11.6%). CONCLUSION: Seropositivity was associated with increased effectiveness of non-TNFi bDMARDs, especially RTX and ABA, but not TNFis.

• Klíčová slova
• ACPA, PANABA, TOCERRA, anti-citrullinated protein antibodies, drug retention, rheumatoid arthritis, rheumatoid factor, seropositivity,
• MeSH
• antirevmatika * klasifikace   imunologie   terapeutické užití   MeSH
• biologické přípravky * klasifikace   imunologie   terapeutické užití   MeSH
• lékové interakce imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezinárodní spolupráce MeSH
• monitorování imunologické * metody   statistika a číselné údaje   MeSH
• nenasazení léčby statistika a číselné údaje   MeSH
• posouzení stavu pacienta MeSH
• registrace statistika a číselné údaje   MeSH
• revmatoidní artritida * diagnóza   farmakoterapie   epidemiologie   imunologie   MeSH
• revmatoidní faktor krev   MeSH
• trvání terapie MeSH
• výběr pacientů MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• antirevmatika * MeSH
• biologické přípravky * MeSH
• revmatoidní faktor MeSH

OBJECTIVE: In an eHealth setting, to investigate intra- and interrater reliability and agreement of joint assessments and Disease Activity Score using C-reactive protein (DAS28-CRP) in patients with rheumatoid arthritis (RA) and test the effect of repeated joint assessment training. METHODS: Patients with DAS28-CRP ≤ 5.1 were included in a prospective cohort study (clinicaltrials.gov: NCT02317939). Intrarater reliability and agreement of patient-performed joint counts were assessed through completion of 5 joint assessments over a 2-month period. All patients received training on joint assessment at baseline; only half of the patients received repeated training. A subset of patients was included in an appraisal of interrater reliability and agreement comparing joint assessments completed by patients, healthcare professionals (HCP), and ultrasonography. Cohen's κ coefficients and intraclass correlation coefficients (ICC) were used for quantifying of reliability of joint assessments and DAS28-CRP. Agreement was assessed using Bland-Altman plots. RESULTS: Intrarater reliability was excellent with ICC of 0.87 (95% CI 0.83-0.90) and minimal detectable change of 1.13. ICC for interrater reliability ranged between 0.69 and 0.90 (good to excellent). Patients tended to rate DAS28-CRP slightly higher than HCP. In patients receiving repeated training, a mean difference in DAS28-CRP of -0.08 was observed (limits of agreements of -1.06 and 0.90). After 2 months, reliability between patients and HCP was similar between groups receiving single or repeated training. CONCLUSION: Patient-performed assessments of joints and DAS28-CRP in an eHealth home-monitoring solution were reliable and comparable with HCP. Patients can acquire the necessary skills to conduct a correct joint assessment after initial and thorough training. [clinicaltrials.gov (NCT02317939)].

• Klíčová slova
• DISEASE ACTIVITY SCORE, HOME MONITORING, RELIABILITY, RHEUMATOID ARTHRITIS, SELF-MANAGEMENT,
• MeSH
• kohortové studie MeSH
• lidé MeSH
• prospektivní studie MeSH
• reprodukovatelnost výsledků MeSH
• revmatoidní artritida * diagnóza   MeSH
• stupeň závažnosti nemoci MeSH
• technologie dálkového snímání * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH

OBJECTIVE: To examine the association of the evolution in physician-reported and patient-reported outcomes with decision to stop biological DMARDs (bDMARDs) in RA. The contribution of baseline characteristics is well established, but little is known about how the disease evolution influences the decision to discontinue therapy. METHODS: RA patients who initiated a bDMARD treatment from 2009 and with information on date of visit were pooled from seven European RA registers. Each outcome was divided into baseline assessments (capturing the inter-individual differences at drug initiation) and changes from baseline at subsequent visits (capturing the individual evolution). Cox regression models were used to examine their association with drug discontinuation, adjusting for baseline patient and co-therapy characteristics and stratifying by register and calendar year of drug initiation. RESULTS: A total of 25 077 patients initiated a bDMARDs (18 507 a TNF-inhibitor, 3863 tocilizumab and 2707 abatacept) contributing an amount of 46 456.8 patient-years. Overall, drug discontinuation was most strongly associated with a poor evolution of the DAS28, with a hazard ratio of 1.34 (95% CI 1.29, 1.40), followed by its baseline value. A change of Physician Global Assessment was the next strongest predictor of discontinuation, then the Patient Global Assessment. CONCLUSIONS: The decision to discontinue treatments appears to be mostly influenced by DAS28 and particularly its evolution over time, followed by Physician Global Assessment evolution, suggesting that the decision to stop bDMARDs relies more on the physician's than on the patient's global assessment.

• Klíčová slova
• DMARDs, abatacept, biological therapies, epidemiology, rheumatoid arthritis, time-varying, tocilizumab, tumour necrosis alpha inhibitors,
• MeSH
• abatacept terapeutické užití   MeSH
• antirevmatika terapeutické užití   MeSH
• časové faktory MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• nenasazení léčby * MeSH
• prospektivní studie MeSH
• registrace * MeSH
• revmatoidní artritida diagnóza   farmakoterapie   epidemiologie   MeSH
• rozhodování * MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Názvy látek
• abatacept MeSH
• antirevmatika MeSH
• humanizované monoklonální protilátky MeSH
• TNF-alfa MeSH
• tocilizumab MeSH Prohlížeč

OBJECTIVE: To assess the long-term safety, tolerability, and effectiveness of tocilizumab (TCZ) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in clinical practice in patients with moderate to severe rheumatoid arthritis (RA). METHODS: Patients in the 24-week, open-label ACT-SURE study who had at least a moderate EULAR response by week 24 and were from a participating country were eligible for this long-term extension (LTE); the patients continued to receive TCZ 8 mg/kg intravenously every 4 weeks as monotherapy or in combination with ≥ 1 csDMARD for up to an additional 108 weeks. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs). Effectiveness endpoints included Disease Activity Score in 28 joints (DAS28) responses, American College of Rheumatology (ACR) responses, and patient-reported outcomes (PROs). RESULTS: Of the 1102 patients who completed the core 24-week study, 934 participated in the LTE; the median exposure to TCZ was 64.3 weeks. From baseline to the end of the LTE, AEs and SAEs occurred in 90% and 9% of patients, respectively. The overall event rates (95% CI) of AEs and SAEs were 406.5 per 100 patient-years (PY) (395.5, 417.8) and 8.8 per 100 PY (7.3, 10.6), respectively. Mean (SD) improvement in DAS28 was 4.12 (1.18), P < 0.0001. The DAS28 remission rates, ACR response rates, and PRO scores were maintained during the LTE study. CONCLUSION: In clinical practice, TCZ as monotherapy or in combination with csDMARDs was safe, well tolerated, and efficacious in patients with moderate to severe RA.

• Klíčová slova
• Monotherapy, Rheumatoid arthritis, Safety, Tocilizumab,
• MeSH
• antirevmatika škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• glukokortikoidy škodlivé účinky   terapeutické užití   MeSH
• humanizované monoklonální protilátky škodlivé účinky   terapeutické užití   MeSH
• inhibitory TNF škodlivé účinky   terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• revmatoidní artritida diagnóza   farmakoterapie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antirevmatika MeSH
• glukokortikoidy MeSH
• humanizované monoklonální protilátky MeSH
• inhibitory TNF MeSH
• tocilizumab MeSH Prohlížeč