OBJECTIVES: To compare the drug survival of etanercept to monoclonal tumour necrosis factor-α inhibitors in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. METHODS: Patients initiating first line biological therapy with tumour necrosis factor-α were propensity score matched and compared for drug survival with a Kaplan-Meier analysis. RESULTS: We matched 657 to 657 patients in rheumatoid arthritis, the median survival time on etanercept was 44.6 months vs. 36.8 months on monoclonal antibody tumour necrosis factor-α inhibitors, with a hazard ratio of 0.94, p = 0.416 We matched 187 to 356 patients in ankylosing spondylitis, the median survival time on etanercept was 75.1 compared to 68.0 months, hazard ratio of 0.78, p = 0.087 We matched 81 to 160 psoriatic arthritis patients, the median survival time on etanercept was 35.8. compared to 65.7 months, hazard ratio 1.61, p = 0.011. Patients treated with etanercept had significantly worse psoriasis scoring during follow up. CONCLUSIONS: We found comparable survival in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis, we found significantly shorter survival on etanercept, possibly due to worse response of skin and nail manifestations.
- MeSH
- adalimumab terapeutické užití MeSH
- ankylózující spondylitida * farmakoterapie mortalita MeSH
- antirevmatika * terapeutické užití MeSH
- dospělí MeSH
- etanercept * terapeutické užití MeSH
- infliximab terapeutické užití MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- monoklonální protilátky terapeutické užití MeSH
- psoriatická artritida * farmakoterapie mortalita MeSH
- registrace * MeSH
- revmatoidní artritida * farmakoterapie mortalita MeSH
- senioři MeSH
- tendenční skóre * MeSH
- TNF-alfa * antagonisté a inhibitory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- adalimumab MeSH
- antirevmatika * MeSH
- etanercept * MeSH
- infliximab MeSH
- monoklonální protilátky MeSH
- TNF-alfa * MeSH
Rheumatoid arthritis and osteoarthritis both affect the articular cartilage, and are characterized by signs and symptoms that can affect the functions of the human body. This cross-sectional observational study evaluated electromyographic activity in the masseter and temporalis muscles, molar bite force, and mandibular mobility in adult women with rheumatoid arthritis or osteoarthritis. A total of 42 women were distributed into 3 groups: rheumatoid arthritis group (ARG, n=14); osteoarthritis group (OAG, n=14); and a healthy control group (CG, n=14). Electromyography was used to evaluate mandibular tasks at rest, right and left laterality, protrusion, and dental clenching during maximum voluntary contraction, with and without parafilm, and a dynamometer was used to analyse the right and left molar bite forces. A digital caliper was used to measure the range of mandibular movement for maximum mouth opening, right and left laterality, and protrusion. Statistical analyses were performed, including analysis of variance and Tukey's test (P<0.05). Electromyography showed no significant differences between the groups when evaluating the masticatory muscles during the mandibular tasks. Significant difference was observed between the ARG and CG, however, in the maximum right (P=0.007) and left (P=0.02) molar bite forces. Significant difference was observed in the maximum mouth opening of the ARG and OAG groups compared with that of the CG (P=0.009), suggesting that adult women with rheumatoid arthritis or osteoarthritis experience functional alterations in the stomatognathic system, particularly in molar bite force and maximum mouth opening.
- Klíčová slova
- Bite force, Electromyography, Mandibular mobility, Masticatory muscles, Osteoarthritis, Rheumatoid arthritis,
- MeSH
- dospělí MeSH
- elektromyografie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mandibula patofyziologie MeSH
- musculus masseter patofyziologie MeSH
- musculus temporalis patofyziologie MeSH
- osteoartróza * patofyziologie diagnóza MeSH
- průřezové studie MeSH
- revmatoidní artritida * patofyziologie MeSH
- senioři MeSH
- síla skusu * MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
INTRODUCTION: Glucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood. METHODS: We investigated long-treated patients with RA (n = 72, median disease duration 14 years) through blood counts and the serum levels of 92 inflammation-related proteins, and disease activity was assessed using the Simple Disease Activity Index (SDAI). Patients were grouped based on the cumulative GC dose, with a cut-off value of 20 g (low/high, n = 49/23). RESULTS AND DISCUSSION: Patients with a high cumulative GC dose within the active RA group had elevated serum levels in 23 inflammation-related proteins compared with patients with a low dose (cytokines/soluble receptors: CCL3, CCL20, CCL25, IL-8, CXCL9, IL-17A, IL-17C, IL-18, sIL-18R1, IL-10, sIL-10RB, OSM and sOPG; growth factors: sTGFα and sHGF; other inflammatory mediators: caspase 8, STAMBP, sCDCP1, sirtuin 2, 4E-BP1, sCD40, uPA and axin-1; pcorr < 0.05). In non-active RA, the high and low GC groups did not differ in analysed serum protein levels. Moreover, patients with active RA with a high GC dose had an increased white blood cell count, increased neutrophil-lymphocyte and platelet-lymphocyte ratios and a decreased lymphocyte-monocyte ratio compared with the low dose group (p < 0.05). This is the first study to report elevated serum levels in inflammation-related proteins and deregulated blood counts in patients with active RA with a high cumulative GC dose. The elevated systemic inflammation highlights the importance of improving care for patients receiving high cumulative GC doses.
- Klíčová slova
- adverse effects of glucocorticoids, autoimmune diseases, blood cell count, cytokine profile, disease activity, long-treated patients, serum protein pattern, systemic inflammation,
- MeSH
- biologické markery krev MeSH
- cytokiny krev MeSH
- dospělí MeSH
- glukokortikoidy * aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mediátory zánětu * krev metabolismus MeSH
- revmatoidní artritida * farmakoterapie krev imunologie MeSH
- senioři MeSH
- zánět MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- cytokiny MeSH
- glukokortikoidy * MeSH
- mediátory zánětu * MeSH
OBJECTIVES: Patients suffering from rheumatoid arthritis (RA) are repeatedly affected by oral diseases or problems, including dental caries and periodontal diseases (PDs). Periodontitis and rheumatoid arthritis are chronic inflammatory destructive diseases that share many similarities. The objective of this study was to assess oral health status including examination of hard dental tissues and periodontium in patients with rheumatoid arthritis and compare the results with healthy controls. We hypothesize some interlink between oral diseases and RA. METHODS: The epidemiological case-control study involved a total of 64 subjects divided into an experimental group (14 rheumatoid arthritis cases) and a control group (50 healthy individuals). Disease activity in the subjects with RA was assessed by the Disease Activity Score (DAS28). The number of Decayed, Missing and Filled Teeth (DMFT) and Community Periodontal Index of Treatment Need (CPITN) as a basic epidemiological oral health indexes were recorded. Finally, the data were analysed statistically. RESULTS: The RA patients (19.21, SD = 6.95) showed a higher caries index level measured by DMFT than the control group (17.72, SD = 6.19); the difference was not statistically significant (U = 387.5, p = 0.547). In terms of a mean number of teeth decayed (p = 0.078), teeth filled due to caries (p = 0.397), and missing teeth (p = 0.126), the two groups were not significantly different. In terms of periodontal health, a significant difference was observed between the two groups concerning the CPI maximum score (p = 0.003). The RA patients showed higher prevalence of periodontitis than the controls. CONCLUSIONS: A complete basic oral examination, along with an oral health instruction including adequate oral and dental hygiene, is crucial to prevent dental caries and periodontal diseases and associated complications in RA patients, since they appear to be more vulnerable than the non-RA population.
- Klíčová slova
- DMFT, oral health, periodontitis, rheumatoid arthritis, tooth decay,
- MeSH
- DMF Index MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci parodontu epidemiologie MeSH
- orální zdraví * statistika a číselné údaje MeSH
- revmatoidní artritida * epidemiologie MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- zubní kaz * epidemiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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.
- Klíčová slova
- ACPA, NK cells, arthralgia, pre-RA,
- 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
- Názvy látek
- protilátky proti citrulinovaným peptidům * MeSH
BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.
- Klíčová slova
- Antirheumatic Agents, Arthritis, Rheumatoid, Biological Therapy, Epidemiology,
- MeSH
- antirevmatika * terapeutické užití MeSH
- azetidiny * MeSH
- inhibitory Janus kinas * terapeutické užití MeSH
- inhibitory TNF terapeutické užití MeSH
- lidé MeSH
- puriny * MeSH
- pyrazoly * MeSH
- revmatoidní artritida * farmakoterapie MeSH
- sulfonamidy * MeSH
- TNF-alfa MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Názvy látek
- antirevmatika * MeSH
- azetidiny * MeSH
- baricitinib MeSH Prohlížeč
- inhibitory Janus kinas * MeSH
- inhibitory TNF MeSH
- puriny * MeSH
- pyrazoly * MeSH
- sulfonamidy * MeSH
- TNF-alfa MeSH
The present study was conducted to scrutinize the pharmacological effect of Estragole (ESG) against CFA-induced arthritis in rats. The rats underwent induction of arthritis using the administration of CFA and after that, the rats were randomly divided into five different groups, where three groups correspond to diverse dosages of ESG, and the other two were control and CFA-arthritic control. Results of the study suggested that ESG in a dose-dependent manner, improves body weight and arthritis score of rats as evidenced by reduction of hind-paw volume. ESG also improved the antioxidant status of rats by reducing MDA levels and enhancing the concentration of endogenous antioxidants SOD and GPx. The level of pro-inflammatory cytokines was also found to be reduced in the case of ESG treated group as compared to CFA-group. In a western blot analysis, ESH showed downregulation of p-JAK-2/STAT-3. The study provided concrete evidence for the protective effect of ESG against rheumatoid arthritis in rats.
- MeSH
- allylbenzenové deriváty * MeSH
- anisoly * MeSH
- antioxidancia farmakologie terapeutické užití MeSH
- artritida experimentální * chemicky indukované farmakoterapie MeSH
- cytokiny metabolismus MeSH
- krysa rodu Rattus MeSH
- potkani Wistar MeSH
- revmatoidní artritida * chemicky indukované farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- allylbenzenové deriváty * MeSH
- anisoly * MeSH
- antioxidancia MeSH
- cytokiny MeSH
- estragole MeSH Prohlížeč
The objective of this study was to evaluate whether RSV inhibits neutrophil extracellular traps (NETs) that induce joint hyperalgesia in C57BL/6 mice after adjuvant-induced arthritis. A subplantar injection of Freund's complete adjuvant was administered to C57BL/6 mice on day 0 for immunization in the AIA model. Resveratrol (RSV, 25 mg/kg) was administered intraperitoneally once daily starting on day 22 and continuing for two weeks. The effects of mechanical hyperalgesia and edema formation have been assessed in addition to histopathological scoring. Mice were sacrificed on day 35 to determine cytokine levels and PADI4 and COX-2 expression levels. ELISA was used to quantify neutrophil extracellular traps (NETs) along with neutrophil elastase-DNA and myeloperoxidase-DNA complexes in neutrophils. An immunohistochemical stain was performed on knee joints to determine the presence of nuclear factor kappa B p65 (NF-kappaB p65). AIA mice were found to have higher levels of NET in joints and their joint cells demonstrated an increased expression of the PADI4 gene. Treatment with RSV in AIA mice (25 mg/kg, i.p.) significantly (P<0.05) inhibited joint hyperalgesia, resulting in a significant increase in mechanical threshold, a decrease in articular edema, a decrease in the production of inflammatory cytokines, increased COX-2 expression, and a decrease in the immunostaining of NF-kappaB. Furthermore, treatment with RSV significantly reduced the amount of neutrophil elastase (NE)-DNA and MPO-DNA complexes, which were used as indicators of NET formation (P<0.05). This study indicates that RSV reduces NET production and hyperalgesia by reducing inflammation mediated by PADI4 and COX-2. According to these data, NETs contribute to joint pain and resveratrol can be used to treat pain in RA through this pathway.
- MeSH
- cyklooxygenasa 2 MeSH
- cytokiny metabolismus MeSH
- DNA metabolismus MeSH
- edém metabolismus MeSH
- extracelulární pasti * metabolismus MeSH
- hyperalgezie farmakoterapie metabolismus MeSH
- leukocytární elastasa metabolismus farmakologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neutrofily metabolismus MeSH
- NF-kappa B metabolismus MeSH
- resveratrol farmakologie terapeutické užití metabolismus MeSH
- revmatoidní artritida * metabolismus MeSH
- toll-like receptor 4 metabolismus MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cyklooxygenasa 2 MeSH
- cytokiny MeSH
- DNA MeSH
- leukocytární elastasa MeSH
- NF-kappa B MeSH
- resveratrol MeSH
- toll-like receptor 4 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
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- abatacept MeSH
- antirevmatika * 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.
- Klíčová slova
- Exercise, Holistic care, Microbiota, Nutrition, Prevention, Rheumatoid arthritis,
- 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
- Názvy látek
- autoprotilátky MeSH