Cardiovascular Risk in Rheumatoid Arthritis

Rheumatoid arthritis (RA), one of the most common inflammatory rheumatic diseases. It is defined as a chronic destructive and deforming arthropathy; it also finds its expression through systemic manifestations. RA has an undulating evolution, with remissions and relapses. Atherosclerotic cardiovascular disease represents one of the most common extra-articular manifestations of RA. It is known that the cardiovascular (CV) morbidity and mortality represent one of the leading causes of reduced life expectancy in RA. Patients with RA develop a premature and accelerated atherosclerosis, explaining the high incidence and prevalence of angina, myocardial infarction, congestive heart failure, stroke, peripheral artery disease, and the need for revascularization. Traditional risk factors (arterial hypertension, obesity, smoking, dyslipidemia, insulin resistance and metabolic syndrome, diabetes mellitus, male gender, physical inactivity) interplay with RA-related risk factors, generating endothelial dysfunction, arterial stiffness, carotid plaque, and atherosclerosis. Traditional cardiovascular risk factors alone cannot explain the increased incidence of premature and accelerated atherogenesis. Chronic inflammation, hyperhomocysteinemia, and hypercoagulation act as novel cardiovascular risk factors. Rheumatoid inflammation exerts direct effects on vessels, or by means of altered traditional risk factors. Antirheumatic drugs may promote atherogenesis or by reducing systemic inflammation may decrease cardiovascular risk. EULAR recommendations require annual cardiovascular risk assessment.

The Risk of Cardiovascular Diseases in Axial Spondyloarthritis. Current Insights

There is an increased cardiovascular (CV) risk in axial spondyloarthritis (axSpA), leading to increased CV mortality and morbidity in these patients. The factors that may explain this enhanced CV risk in axSpA are multiple, including traditional CV risk factors such as smoking, but also the inflammatory process and probably the use of non-steroidal anti-inflammatory drugs (NSAIDs). The CV involvement of axSpA may be detected at an early and pre-clinical stage, using non-invasive techniques. While NSAIDs play a deleterious role in the CV risk of axSpA, TNF inhibitors seem to have a beneficial impact, but this remains to be demonstrated in specific clinical studies. More data are needed to determine the potential effects of IL-17 inhibitors on the CV risk of axSpA. CV comorbidity has been mainly assessed in the radiographic form of axSpA, while limited data are available in patients with the non-radiographic form. The current management of axSpA must consider this CV comorbidity according to the EULAR recommendations. Rheumatologists play a determinant role in the detection of CV risk and current management of these patients is focused on the control of disease activity, suppression of inflammation, screening for and management of traditional CV risk factors, as well as the restriction of NSAID use.

Ultrasound features of Achilles enthesitis in psoriatic arthritis: a systematic review

Objectives The objectives were to evaluate the methodological and reporting quality of ultrasound (US) studies of Achilles enthesitis in people with psoriatic arthritis (PsA), to identify the definitions and scoring systems adopted and to estimate the prevalence of ultrasound features of Achilles enthesitis in this population. Methods A systematic literature review was conducted using the AMED, CINAHL, MEDLINE, ProQuest and Web of Science databases. Eligible studies had to measure US features of Achilles enthesitis in people with PsA. Methodological quality was assessed using a modified Downs and Black Quality Index tool. US protocol reporting was assessed using a checklist informed by the European League Against Rheumatism (EULAR) recommendations for the reporting of US studies in rheumatic and musculoskeletal diseases. Results Fifteen studies were included. One study was scored as high methodological quality, 9 as moderate and 5 as low. Significant heterogeneity was observed in the prevalence, descriptions, scoring of features and quality of US protocol reporting. Prevalence estimates (% of entheses) reported included hypoechogenicity [mean 5.9% (s.d. 0.9)], increased thickness [mean 22.1% (s.d. 12.2)], erosions [mean 3.3% (s.d. 2.5)], calcifications [mean 42.6% (s.d. 15.6)], enthesophytes [mean 41.3% (s.d. 15.6)] and Doppler signal [mean 11.8% (s.d. 10.1)]. Conclusions The review highlighted significant variations in prevalence figures that could potentially be explained by the range of definitions and scoring criteria available, but also due to the inconsistent reporting of US protocols. Uptake of the EULAR recommendations and using the latest definitions and validated scoring criteria would allow for a better understanding of the frequency and severity of individual features of pathology.

Efficacy and safety of intra-articular therapies in rheumatic and musculoskeletal diseases: an overview of systematic reviews

ObjectiveTo summarise the evidence on intra-articular therapies (IAT) to inform the 2020 EULAR recommendations.MethodsAn overview of systematic reviews (SR) including randomised-controlled trials (RCTs) of IAT in adults with arthropathies was performed up to July 2020. Pain, function, and frequency of adverse events were the main efficacy and safety outcomes, respectively. Quality was assessed with the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool.ResultsOf 184 references identified, 16 met the inclusion criteria, and a search of their reference lists identified 16 additional SRs. After quality assessment, 29 were finally included. Of these, 18 focused on knee osteoarthritis (KOA), 6 on hip osteoarthritis (HOA), 3 on shoulder capsulitis (SC), and 3 on rheumatoid arthritis. Overall, hyaluronic acid showed a small effect on pain and function in KOA but not in HOA or shoulder capsulitis. Intra-articular glucocorticoids showed a small effect in pain and function in KOA and function in HOA and SC. Platelet-rich plasma showed benefit in pain and function in KOA but not in HOA. Mesenchymal stem cells behaved similarly. Most SR results were of moderate quality and RCTs included often presented a high risk of bias, mainly due to inadequate blinding and heterogeneous results. All interventions were well tolerated with no clear safety differences.ConclusionsThis overview underlines that most IAT currently used in KOA, HOA, and SC exert small effects and are well tolerated. However, no firm conclusions can be drawn for inflammatory arthritis due to the limited data found.

EULAR recommendations for intra-articular therapies

ObjectivesTo establish evidence-based recommendations to guide health professionals using intra-articular therapies (IAT) in adult patients with peripheral arthropathies.MethodsA multidisciplinary international task force established the objectives, users and scope and the need for background information, including systematic literature reviews) and two surveys addressed to healthcare providers and patients throughout Europe. The evidence was discussed in a face-to-face meeting, recommendations were formulated and subsequently voted for anonymously in a three-round Delphi process to obtain the final agreement. The level of evidence was assigned to each recommendation with the Oxford levels of evidence.ResultsRecommendations focus on practical aspects to guide health professionals before, during and after IAT in adult patients with peripheral arthropathies. Five overarching principles and 11 recommendations were established, addressing issues related to patient information, procedure and setting, accuracy, routine and special aseptic care, safety issues and precautions to be addressed in special populations, efficacy and safety of repeated joint injections, use of local anaesthetics and aftercare.ConclusionWe have developed the first evidence and expert opinion-based recommendations to guide health professionals using IAT. We hope that these recommendations will be included in different educational programmes, used by patient associations and put into practice via scientific societies to help improve uniformity and quality of care when performing IAT in peripheral adult joints.

POS0764 EULAR RECOMMENDATION-BASED QUALITY INDICATORS (QIS) FOR SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): ELABORATION, FINAL SET, PERFORMANCE AND INITIAL VALIDATION

Background:Targets of therapy and quality of care are receiving increased attention in systemic lupus erythematosus (SLE).Objectives:To develop Quality Indicators (QIs) for the care of SLE patients based on the EULAR recommendations, and assess their performance.Methods:Using the published EULAR recommendations for SLE, we developed 44 candidate QIs. These were independently rated for validity and feasibility by 12 experts, analysed by a modified RAND/UCLA model and further scrutinized based on the scorings and expert opinion. (Fig.1) Adherence to the final set of QIs was tested in a cohort of 220 SLE patients combined with an assessment on its impact on disease outcomes such as flares, hospitalizations and organ damage.Results:The panel rated 18 QIs as valid and feasible. These involve diagnosis; disease and damage assessment; monitoring for lupus nephritis and drug toxicity; therapy and targets of therapy; fertility and pregnancy; and adjunct therapy (preventive measures for osteoporosis, vaccination, cardiovascular disease). On average, SLE patients received 54% (95%CI 52–56%) of the indicated care with adherence ranging from 41% for QIs related to monitoring to 88% for treatment-related QIs. Regarding targets of therapy, sustained remission or low disease activity were achieved in 27%, while 94% of patients received low-dose glucocorticoids, and 92% the recommended hydroxychloroquine dose. Dependent upon individual QI tested, adherence for lupus nephritis-related QIs was 88% for receiving appropriate adjunct therapy (ACE inhibitors) to 100% for being treated with the indicated immunosuppressive treatment. In contrast, adherence to QIs related to preventive measures and other adjunct therapies was moderate to low. Notably, patients who were eligible for cardiovascular risk modification, vaccination, and osteoporosis management received lower quality of care (40.5%, 47.7% and 45.5% respectively) while 91.4% had sunscreen protection. In reference to laboratory work-up and monitoring, complete laboratory work-up at diagnosis was performed in 48%, while disease activity and damage, were fully assessed only in 14.1% (in three consecutive visits) and 28.6% (annually) respectively, Similarly, reproductive health and pregnancy counselling adherence rates were modest estimated at 50% and 62% respectively. Higher adherence to the indicated care during follow-up (monitoring QIs) was associated with reduced risk for adverse outcomes during the last year of observation (OR 0.97, 95%CI 0.96-0.99). Patients who achieved sustained remission or LLDAS, exhibited fewer flares (OR=0.15, p-value<0.001) and damage accrual (OR=0.35, p-value<0.001). Of interest, patients who received low-dose of GCs or were appropriately vaccinated, had a lower risk of experiencing a flare (OR=0.23 and 0.46 respectively).Conclusion:A set of 18 QIs based on the EULAR recommendations for SLE was developed to be used towards improving care in SLE. Initial real-life data suggest variable degree of adherence with higher adherence resulting in reduced adverse outcomes.References:[1]Fanouriakis, et al., 2019 Update of the EULAR recommendations for the management of systemic lupus erythematosus. In Annals of the Rheumatic Diseases (Vol. 78, Issue 6, pp. 736–745). BMJ Publishing Group. https://doi.org/10.1136/annrheumdis-2019-215089.[2]Nikolopoulos, D., et al., Evolving phenotype of systemic lupus erythematosus in Caucasians: low incidence of lupus nephritis, high burden of neuropsychiatric disease and increased rates of late-onset lupus in the ‘Attikon’ cohort. Lupus, 29(5), 514–522. https://doi.org/10.1177/0961203320908932.Acknowledgements:This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 742390)Disclosure of Interests:None declared

AB0541 PREDICTING THE INITIATION OF BIOLOGIC DMARDS IN EARLY PSORIATIC ARTHRITIS WITHIN 1-YEAR OF TREAT-TO-TARGET STRATEGY

Background:According to the EULAR recommendations and treat-to-target (T2T) strategy synthetic (s) DMARDs are the first-line of PsA therapy and biologic (b) DMARDs are the second one [1]. The value of early intervention by bDMARDs in PsA has been demonstrated recently [2]. But factors which can predict bDMARDs initiation have not been evaluated yet.Objectives:To identify prognostic factors for initiation of bDMARDs within 1-year of T2T strategy in early PsA.Methods:70 patients (pts) (M/F=35/35) with active early PsA fulfilling the CASPAR criteria treated by T2T strategy were included. Mean age 36.9±10.2 years (yrs), PsA duration 11.3±10.6 months (mos.), psoriasis duration 80.6±89.9 mos. Median DAPSA= 29.4 [23.1;36.0]. At baseline (BL) all pts were given therapy with Methotrexate (MTX) s/c with escalating dose from 5 to 25 mg/wk, then over a period of 12 mos pts with ineffectiveness of MTX were added bDMARDs. At BL and every 3 month of therapy all pts underwent standard clinical examinations of PsA activity. DAPSA, ESR (mm/h), CRP (mg/l), the number of pts with dactylitis, enthesitis by LEI and plantar fascia, BSA (%), HAQ and fatigue by FACIT (Functional Assessment of Chronic Illness Therapy) Fatigue Scale (Version 4), BMI (kg/m2) were evaluated. DAPSA > 28 indicate high activity, a score FACIT < 30 - severe fatigue, BMI >25 overweight and obese. At 12 mos. pts were divided into two groups. Group 1 included 42 pts who were treated with MTX only and group 2 - 28 pts those with added bDMARDs during 12 mos. Multi-dimensional step-by-step discriminant analysis was used to identify a group of signs associated with the need to initiate bDMARDs within 12 mos.Results:Comparative analysis of two groups showed the following features proved to be the most informative at BL and at 3 mos. of sDMARDs therapy with MTX: high PsA activity by DAPSA ≥ 30 (р = 0.009), BMI (kg/m2) ≥ 27 (р = 0.019), entesitis ≥ 1 (p= 0.005), ESR ≥ 20 mm/h (p= 0.007), FACIT < 30 (p= 0.074), male sex (р = 0.098). Early PsA pts with combination of these features at the first visit and at 3 mos. of MTX monotherapy have more chance to initiate bDMARDs in comparison to pts without them. Area Under ROC Curve (AUC) 0.892; 95% CI (0.818-0.966). Sensitivity/ Specificity of model 82% / 76% accordingly. (Figure 1).Figure 1.Conclusion:It is a combination of features from first visit to clinic and at 3 mos. of MTX monotherapy – high PsA activity by DAPSA, male gender, persistent entesitis, obesity, ESR increase and severe fatigue by FACIT - that constitutes a prognostic factor for the initiation of bDMARDs at an early-stage of PsA. These factors should be considered in clinical practice to avoid losing time for the early initiation of bDMARDs and improved outcomes of PsA.References:[1]Gossec L, et al. Ann Rheum Dis. 2020;79:700–712. doi:10.1136/annrheumdis-2020-217159. 2. van Mens LJJ, et al. Ann Rheum Dis 2019;78:610–616. doi:10.1136/annrheumdis-2018-214746Disclosure of Interests:None declared.

POS1423 LIFESTYLE HABITS IN PATIENTS WITH RHEUMATOID ARTHRITIS – A CROSS SECTIONAL STUDY ON TWO SCANDINAVIAN COHORTS

Background:In people with rheumatoid arthritis (RA), modifiable lifestyle factors such as smoking, being overweight/obese, alcohol overuse and physical inactivity may not only affect treatment response and quality of life, but can also increase the risk for cardio-vascular diseases and other comorbidities (1,2). Evidence and EULAR guidelines (3) support lifestyle changes in patients with RA. If a patient need to change several habits, the challenge may seem overwhelming and substantial support will be needed. There is little information concerning the prevalence of a combined number of unhealthy lifestyle (UL) factors in people with RA.Objectives:I) To study the prevalence of unhealthy lifestyle factors in two Scandinavian RA cohorts. II) To study the association between disease impact and two or more unhealthy lifestyle factors.Methods:Patients diagnosed with RA who participated in a cardiovascular screening consultation at a specialist clinic during 2016-2018 and responded to four lifestyle questions, constituted the Danish cohort (data retrieved from the national registry DANBIO). Patients with RA belonging to the BARFOT cohort, and who in a 2017 survey responded to four lifestyle questions, constituted the Swedish cohort. Lifestyle information was dichotomized as present tobacco use or not, BMI <25 kg/m2 vs. ≥25 kg/m2, alcohol overuse or not, and health enhancing physical activity (≥ 150 minutes/week) or less. The combined number of UL factors (0, 1, 2, 3, 4) were calculated. Crude logistic regression analyses were performed to determine the association between disease impact and two or more UL factors (controlled for age, gender and disease duration). Independent factors (disease impact) were pain (NRS 0-10, best to worst), fatigue (NRS 0-10, best to worst), function (HAQ, 0-3, best to worst) and quality of life (EQ-5D-3L 0-1, worst to best).Results:The 566 included Danish patients had a mean age of 61.82 (SD 11.13) years, a disease duration of mean 12.40 (SD 10.95) years, and 72% were women. The 995 Swedish patients had a mean age of 66.38 (SD 12.90) years, a disease duration of mean 15.55 (SD 3.85) years, and 72% were women. 95% of the Danish patients and 82% of the Swedish patients reported at least one UL factor, while 66% and 47% respectively reported two or more (Figure 1). The most common ones were overweight/obesity and physical inactivity in both cohorts. Male gender OR 1.86 95% CI [1.21-2.85] and shorter disease duration OR 0.97 95% CI [0.95-0.99] were associated with two or more UL factors in the Danish cohort. In the Swedish cohort, male gender OR 1.42 95% CI [1.07 – 1.89], worse pain OR 1.10 95% CI [1.04 – 1.15], fatigue OR 1.09 95% CI [1.04 – 1.15], function OR 1.64 95% CI [1.28 – 2.10], and worse quality of life OR 0.35 95% CI [0.20 – 0.60] were associated with two or more UL factors.Conclusion:Every other patient with RA had two or more UL factors in both the Danish and Swedish cohort, and more often they were men. The combined number of UL factors was not necessarily associated with disease impact. The findings are important for health professionals working with lifestyle interventions in patients with RA.Figure 1.The combined number of unhealthy lifestyle (UL) factors in two Scandinavian RA cohorts.References:[1]Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685-99.[2]Lindhardsen J, Ahlehoff O, Gislason GH, Madsen OR, Olesen JB, Torp-Pedersen C, et al. The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study. Ann Rheum Dis. 2011;70(6):929-34.[3]Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes IB, Peters MJ, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017;76(1):17-28.Disclosure of Interests:None declared

POS1368 ANTI-IL-1 THERAPIES IN COLCHICINE-RESISTANT OR İNTOLERANT PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER: SINGLE CENTER EXPERIENCE

Background:Familial Mediterranean Fever (FMF) is a hereditary auto-inflammatory disease characterized by recurrent fever and serosal inflammation (1). The goal of FMF treatment is to prevent the attacks and to minimize subclinical inflammation between attacks The main treatment of FMF is colchicine however anti-interleukin-1 treatments are recommended in colchicine resistant and/or intolerant FMF patients (2).Objectives:The aim of this study is to evaluate the efficacy of anti-interleukin-1 (anti-IL-1) agents in 81 FMF patients with resistant/intolareted to colchicine or complicated with amyloidosis.Methods:Between January 2014 and December 2020, eighty-one patients who were diagnosed as FMF according to the criteria of Tel-Hashomer that following-up at Cumhuriyet University Medical Faculty Rheumatology-Internal Medicine Department were included in to the study.Results:45 (55.6%) male and 36 (44.4%) female were included in the study. The median age of the patients was 25 years (min:17-max: 60) and the median age at diagnosis was 15 years (min 3-max 46). 44 patients (54.3%) used Anakinra (100 mg/day), and 27 (45.7%) canakinumab (150mg/8month) were used. 49 cases were resistant to colchicine,16 were intolerant to colchicine, 16 (20%) cases were comlicated with amyloidosis. 10 patients had renal transplantation. MEFV gene mutations are shown in Table 1. Median duration of anti-IL-1 agent use was 24 month (min:4-max 52). 9 patients were resistant to anakinra, 18 patients had side effects which anakinra related. After a median follow up 12 months overall clinical response was %95 (frequency of attacks <1/6months). median proteinuria decreased from 3500 mg /day to median 1500 mg /day (p: 0.04) (Table 2). IL-6 treatment was started in 4 patients because of ineffective canakinumab. Five pregnant patients were followed up with anakinra during pregnancy and there were no problems.Conclusion:Anti-interleukin-1 agents are effectively and safely in the treatment of FMF patients. There are still unanswered questions in FMF treatment such as other factors affecting the frequency of attacks, colchicine resistance is not defined precisely and the importance of some mutations. The effect of anti IL-1 agents on FMF patients with amyloidosis is not clearly. According to our experience, these treatments are effective in patients with glomerular filtration rate> 60 ml/min. For answers to these and similar questions, Large and long follow-up studies are needed for long-term effects.References:[1]Özen S, Batu ED, Demir S., Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management. Front Immunol. 2017 Mar 23;8:253. doi: 10.3389/fimmu.2017.00253. eCollection 2017.[2]Seza Özen ve ark. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis. 2016 Apr;75(4):644-51.Disclosure of Interests:None declared