Search

Objective: As part of European League against Rheumatism (EULAR)/European Musculoskeletal Conditions Surveillance and Information Network, 20 user-focused standards of care (SoCs) for rheumatoid arthritis (RA) addressing 16 domains of care were developed. This study aimed to explore gaps in implementation of these SoCs across Europe., Methods: Two cross-sectional surveys on the importance, level of and barriers (patients only) to implementation of each SoC (0-10, 10 highest) were designed to be conducted among patients and rheumatologists in 50 European countries. Care gaps were calculated as the difference between the actual and maximum possible score for implementation (ie, 10) multiplied by the care importance score, resulting in care gaps (0-100, maximal gap). Factors associated with the problematic care gaps (ie, gap≥30 and importance≥6 and implementation<6) and strong barriers (≥6) were further analysed in multilevel logistic regression models., Results: Overall, 26 and 31 countries provided data from 1873 patients and 1131 rheumatologists, respectively. 19 out of 20 SoCs were problematic from the perspectives of more than 20% of patients, while this was true for only 10 SoCs for rheumatologists. Rheumatologists in countries with lower gross domestic product and non-European Union countries were more likely to report problematic gaps in 15 of 20 SoCs, while virtually no differences were observed among patients. Lack of relevance of some SoCs (71%) and limited time of professionals (66%) were the most frequent implementation barriers identified by patients., Conclusions: Many problematic gaps were reported across several essential aspects of RA care. More efforts need to be devoted to implementation of EULAR SoCs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Smoking has been connected to citrullination of antigens and formation of anti-citrullinated peptide antibodies (ACPAs) in rheumatoid arthritis (RA). Since smoking can modify proteins by carbamylation (formation of homocitrulline), this study was conducted to investigate these effects on vimentin in animal models and RA., Methods: The efficiency of enzymatic carbamylation of vimentin was characterised. B-cell response was investigated after immunisation of rabbits with different vimentin isoforms. Effects of tobacco smoke exposure on carbamylation of vimentin and formation of autoantibodies were analysed in mice. The antibody responses against isoforms of vimentin were characterised with respect to disease duration and smoking status of patients with RA., Results: Enzymatic carbamylation of vimentin was efficiently achieved. Subsequent citrullination of vimentin was not disturbed by homocitrullination. Sera from rabbits immunised with carbamylated vimentin (carbVim), in addition to carbVim also recognised human IgG-Fc showing rheumatoid factor-like reactivity. Smoke-exposed mice contained detectable amounts of carbVim and developed a broad immune response against carbamylated antigens. Although the prevalence of anti-carbamylated antibodies in smokers and non-smokers was similar, the titres of carbamylated antibodies were significantly increased in sera of smoking compared with non-smoking RA. CarbVim antibodies were observed independently of ACPAs in early phases of disease and double-positive patients for anti-mutated citrullinated vimentin (MCV) and anti-carbVim antibodies showed an extended epitope recognition pattern towards MCV., Conclusions: Carbamylation of vimentin is inducible by cigarette smoke exposure. The polyclonal immune response against modified antigens in patients with RA is not exclusively citrulline-specific and carbamylation of antigens could be involved in the pathogenesis of disease., Trial Registration Number: ISRCTN36745608; EudraCT Number: 2006-003146-41., Competing Interests: Competing interests: HB is an employee of Orgentec Diagnostika GmbH, Mainz, Germany; test kits were kindly provided by Orgentec., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: To compare the value that rheumatologists across Europe attach to patients' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis., Methods: In a discrete choice experiment, European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity. Treatments differed in five attributes: efficacy (improvement and achieved state on disease activity), safety (probability of serious adverse events), patient's preference (level of agreement), medication costs and cost-effectiveness (incremental cost-effectiveness ratio (ICER)). A Bayesian efficient design defined 14 choice sets, and a random parameter logit model was used to estimate relative preferences for rheumatologists across countries. Cluster analyses and latent class models were applied to understand preference patterns across countries and among individual rheumatologists., Results: Responses of 559 rheumatologists from 12 European countries were included in the analysis (49% females, mean age 48 years). In all countries, efficacy dominated treatment decisions followed by economic considerations and patients' preferences. Across countries, rheumatologists avoided selecting a treatment that patients disliked. Latent class models revealed four respondent profiles: one traded off all attributes except safety, and the remaining three classes disregarded ICER. Among individual rheumatologists, 57% disregarded ICER and these were more likely from Italy, Romania, Portugal or France, whereas 43% disregarded uncommon/rare side effects and were more likely from Belgium, Germany, Hungary, the Netherlands, Norway, Spain, Sweden or UK., Conclusions: Overall, European rheumatologists are willing to trade between treatment efficacy, patients' treatment preferences and economic considerations. However, the degree of trade-off differs between countries and among individuals., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: PATIENTS with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions., Objectives: To evaluate the prevalence of comorbidities and compare their management in RA patients from different countries worldwide., Study Design: international, cross-sectional., Patients: consecutive RA patients., Data Collected: demographics, disease characteristics (activity, severity, treatment), comorbidities (cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and psychiatric disorders)., Results: Of 4586 patients recruited in 17 participating countries, 3920 were analysed (age, 56±13 years; disease duration, 10±9 years (mean±SD); female gender, 82%; DAS28 (Disease Activity Score using 28 joints)-erythrocyte sedimentation rate, 3.7±1.6 (mean±SD); Health Assessment Questionnaire, 1.0±0.7 (mean±SD); past or current methotrexate use, 89%; past or current use of biological agents, 39%. The most frequently associated diseases (past or current) were: depression, 15%; asthma, 6.6%; cardiovascular events (myocardial infarction, stroke), 6%; solid malignancies (excluding basal cell carcinoma), 4.5%; chronic obstructive pulmonary disease, 3.5%. High intercountry variability was observed for both the prevalence of comorbidities and the proportion of subjects complying with recommendations for preventing and managing comorbidities. The systematic evaluation of comorbidities in this study detected abnormalities in vital signs, such as elevated blood pressure in 11.2%, and identified conditions that manifest as laboratory test abnormalities, such as hyperglycaemia in 3.3% and hyperlipidaemia in 8.3%., Conclusions: Among RA patients, there is a high prevalence of comorbidities and their risk factors. In this multinational sample, variability among countries was wide, not only in prevalence but also in compliance with recommendations for preventing and managing these comorbidities. Systematic measurement of vital signs and laboratory testing detects otherwise unrecognised comorbid conditions.

Objective: To investigate the long-term effects of induction therapy with adalimumab (ADA) plus methotrexate (MTX) in comparison with placebo (PBO) plus MTX in DMARD-naïve patients with active early rheumatoid arthritis (RA)., Methods: Patients with active early RA (disease duration of ≤12 months) were randomly assigned to receive 40 mg ADA subcutaneously every other week (eow) plus MTX 15 mg/week subcutaneously or PBO plus MTX subcutaneously at 15 mg/week over 24 weeks. Thereafter, all patients received MTX monotherapy up to week 48. The primary outcome was the Disease Activity Score 28 (DAS28) at week 48. Secondary outcomes included proportions of patients in remission (DAS28<2.6), ACR responses, Health Assessment Questionnaire (HAQ) score and radiographic progression., Results: 87 patients were assigned to ADA/MTX and 85 patients to PBO/MTX. At baseline, DAS28 was 6.2±0.8 in the ADA/MTX and 6.3±0.9 in the PBO/MTX groups. At week 24, treatment with ADA/MTX compared with PBO/MTX resulted in a greater reduction in DAS28 (3.0±1.2 vs 3.6±1.4; p=0.009) and other secondary outcomes such as DAS28 remission rate (47.9% vs 29.5%; p=0.021) and HAQ (0.49±0.6 vs 0.72±0.6; p=0.0014). At week 48, the difference in clinical outcomes between groups was not statistically significant (DAS28: 3.2±1.4 vs 3.4±1.6; p=0.41). Radiographic progression at week 48 was significantly greater in patients administered PBO/MTX (Sharp/van der Heijde score: ADA/MTX 2.6 vs PBO/MTX 6.4; p=0.03, Ratingen score: 1.7 vs 4.2; p=0.01)., Conclusions: A greater reduction in radiographic progression after initial combination therapy with ADA and MTX was seen at week 48, even after discontinuation of ADA treatment at week 24. This sustained effect was not found at the primary endpoint (DAS28 reduction).

Objective: The first 3 months after symptom onset represent an important therapeutic window for rheumatoid arthritis (RA). This study investigates the extent and causes of delay in assessment of patients with RA in eight European countries., Method: Data on the following levels of delay were collected from 10 centres (Berlin, Birmingham, Heraklion, Lund, Prague, Stockholm, Umeå, Vienna, Warsaw and Zurich): (1) from onset of RA symptoms to request to see healthcare professional (HCP); (2) from request to see HCP to assessment by that HCP; (3) from initial assessment by HCP to referral to rheumatologist; and (4) from referral to rheumatologist to assessment by that rheumatologist., Results: Data were collected from 482 patients with RA. The median delay across the 10 centres from symptom onset to assessment by the rheumatologist was 24 weeks, with the percentage of patients seen within 12 weeks of symptom onset ranging from 8% to 42%. There were important differences in the levels underlying the total delays at individual centres., Conclusions: This research highlights the contribution of patients, professionals and health systems to treatment delay for patients with RA in Europe. Although some centres have strengths in minimising certain types of delay, interventions are required in all centres to ensure timely treatment for patients.

Objective: Ankylosing spondylitis (AS) and periodontal disease (PD) are characterised by dysregulation of the host inflammatory response, resulting in soft and hard connective tissue destruction. AS has been related to other inflammatory diseases, however, there is a paucity of data on whether AS is associated with inflammatory PD., Methods: The association between AS and PD was examined in 48 patients with AS and 48 healthy controls, matched for age and gender. AS was diagnosed according to the modified New York criteria. Periodontal examination included probing pocket depth (PPD), clinical attachment loss (CAL), plaque index (PI) and bleeding on probing (BOP). Potential risk factors of PD such as smoking, low education, alcohol consumption, body mass index (BMI), as well as chronic diseases associated with PD and AS were assessed through questionnaires., Results: In stepwise logistic regression, including AS status, age, gender, education, smoking, alcohol consumption and BMI, only AS status, age and education remained significant predictors of PD. Patients with AS had significant 6.81-fold increased odds (95% CI 1.96 to 23.67) of PD (defined as mean attachment loss >3 mm) compared to controls. The strength of the association was attenuated but remained statistically significant after further adjustment for plaque accumulation (odds ratio (OR) 5.48, 95% CI 1.37 to 22.00)., Conclusions: The present study shows that patients with AS have a significantly higher risk of PD, strongly suggesting the need for close collaboration between rheumatologists, periodontists and dental hygienists when treating patients with AS.

Background: It has been suggested that bacterial infections have a role in the pathogenesis of rheumatoid arthritis (RA). P gingivalis, a Gram-negative, anaerobic rod, is one of the major pathogens associated with periodontal disease., Objective: To examine P gingivalis infection and its effects on cell cycle progression and apoptosis of human articular chondrocytes., Methods: Primary human chondrocytes cultured in monolayers were challenged with P gingivalis. Infection and invasion of P gingivalis into chondrocytes was analysed by scanning electron microscopy, double immunofluorescence and by antibiotic protection and invasion assay. Cell cycle progression of infected chondrocytes was evaluated by flow cytometry. Also, cell apoptosis was visualised by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) of DNA strand breaks and by western blot analysis., Results: Data showed that P gingivalis could adhere and infect primary human chondrocytes. After chondrocyte infection, intracellular localisation of P gingivalis was noted. Flow cytometry analyses demonstrated affected cell cycle progression, with an increase of the G(1) phase and a significant decrease of the G(2) phase after infection. In addition, increased apoptosis of P gingivalis-infected chondrocytes was visualised by TUNEL assay and by upregulation of caspase-3 protein expression., Conclusion: These data demonstrate that P gingivalis infects primary human chondrocytes and affects cellular responses, which might contribute to the tissue damage seen in the pathogenesis of rheumatoid arthritis.

Objective: To perform a prospective long term follow up study comparing conventional radiography (CR), ultrasonography (US), and magnetic resonance imaging (MRI) in the detection of bone erosions and synovitis in rheumatoid arthritis (RA) finger joints., Methods: The metacarpophalangeal and proximal interphalangeal joints II-V (128 joints) of the clinically dominant hand of 16 patients with RA were included. Follow up joint by joint comparisons for erosions and synovitis were made., Results: At baseline, CR detected erosions in 5/128 (4%) of all joints, US in 12/128 (9%), and MRI in 34/128 (27%). Seven years later, an increase of joints with erosions was found with CR (26%), US (49%) (p<0.001 each), and MRI (32%, NS). In contrast, joint swelling and tenderness assessed by clinical examination were decreased at follow up (p = 0.2, p<0.001). A significant reduction in synovitis with US and MRI (p<0.001 each) was seen. In CR, 12 patients did not have any erosions at baseline, while in 10/12 patients erosions were detected in 25/96 (26%) joints after 7 years. US initially detected erosions in 9 joints, of which two of these joints with erosions were seen by CR at follow up. MRI initially found 34 erosions, of which 14 (41%) were then detected by CR., Conclusion: After 7 years, an increase of bone erosions was detected by all imaging modalities. In contrast, clinical improvement and regression of synovitis were seen only with US and MRI. More than one third of erosions previously detected by MRI were seen by CR 7 years later.