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ObjectiveTo examine the association between psoriatic arthritis (PsA) and all-cause mortality from a large population-based database.MethodsPatients with PsA from the Clalit Health Services database were identified between 2003–2018 and matched to 4 controls by age, sex, ethnicity, and index date. Patient demographics, comorbidities, and treatments were extracted. Mortality data were obtained from the Israeli Notification of Death certificate. The proportionate mortality rate (PMR) of the leading causes of death was calculated and compared to that of the general population. Cox proportional hazard regression models were used to estimate the crude and the multivariate adjusted HR for the association between PsA and all-cause mortality and for factors associated with mortality within the PsA group.ResultsThere were 5275 patients with PsA and 21,011 controls included and followed for 7.2 ± 4.4 years. The mean age was 51.7 ± 15.4 years, and 53% were females. Among patients with PsA, 38.2% were on biologics. Four hundred seventy-one (8.9%) patients died in the PsA group compared to 1668 (7.9%) in the control group. The crude HR for the association of PsA and all-cause mortality was 1.16 (95% CI 1.04–1.29) and 1.02 (95% CI 0.90–1.15) on multivariate analysis. Malignancy was the leading cause of death (26%), followed by ischemic heart disease (15.8%); this is in keeping with the leading causes of death in the general population. Older age, male sex, lower socioeconomic status, increased BMI, increased Charlson comorbidity index scores, and history of psoriasis or hospitalization in 1 year prior to entry were positive predictors for mortality.ConclusionNo clinically relevant increase in mortality rate was observed in patients with PsA, and specific PMRs were similar to those of the general population.

Ofir Elalouf,1,2 Merav Lidar,2,3 Tatiana Reitblat,4 Devy Zisman,5 Alexandra Balbir-Gurman,6 Odelia Hakakian,1 Tanya Mashiach,7 Ronit Almog,7 Ori Elkayam1,2 1Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Rheumatology Unit, The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Ramat Gan, Israel; 4Rheumatology Unit, Barzilai Medical Center, Ashkelon, Israel; 5Department of Rheumatology, Carmel Medical Center, Haifa, Israel; 6Rheumatology Institute; 7Epidemiology and Biostatistics Unit, Rambam Health Care Campus, Haifa, IsraelCorrespondence: Ofir ElaloufDepartment of Rheumatology, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, IsraelTel +972524262682Fax +97235422904Email ofire@tlvmc.gov.ilPurpose: To evaluate the association between body mass index (BMI) and tumor necrosis factor α (TNF-α) blockers retention in patients with rheumatoid arthritis (RA).Patients and Methods: This prospective cohort study analyzed data about patients with RA who initiated TNF blockers from the Israeli registry of inflammatory diseases from 2011 to 2019. Patients were grouped by BMI: normal (BMI < 24.9 kg/m2), overweight (BMI 25– 29.9 kg/m2), obese (BMI 30– 34.9 kg/m2) and morbid obese (BMI ≥ 35 kg/m2). Treatment cessation due to inefficacy was defined as an “event” and therapy with a drug above 3 months was defined as a “course.” Kaplan–Meier survival curve was used to describe drug survival. Event-free survival was calculated using Cox regression with a hazard ratio and confidence interval of 95%.Results: The final analysis included 521 RA patients (80% females) treated with etanercept, infliximab, adalimumab or golimumab. Eight hundred and eighteen treatment initiations were included in the final analysis, 334 (41%) in the normal weight group, 261 (32%) in the overweight, 144 (17%) in the obese and 79 (10%) in the morbid obesity group. Three hundred and twenty-six (40%) treatment initiations were with etanercept, 215 (26%) with adalimumab 197 (24%) with infliximab, and 80 (10%) with golimumab. BMI was inversely associated with drug survival. Morbid obese patients were more likely to discontinue treatment compared with normal weight patients HR 2.28 (95% CI 1.67– 3.10, p< 0.01). This association remained significant for each drug type (except for golimumab) in a subgroup analysis. Adalimumab switch rate was higher compared to etanercept with HR =1.51 (95% CI 1.20– 1.91, p< 0.01), no other significant differences were noted between the other drugs.Conclusion: Morbid obese RA patients have lower TNF-α blocker retention compared to normal weight patients.Keywords: TNF alpha, biologics, BMI, obesity, survival

Background Persistence of biologic therapy in psoriatic arthritis (PsA) patients is an important factor in individualized patient treatment planning and healthcare policy and guideline development. Objective To estimate the persistence of biologic agents prescribed to PsA patients in a real-life setting as well as factors associated with improved biologic drug survival in these patients. Methods Patients with PsA from a large healthcare provider database with at least two consecutive dispensed prescriptions of a biologic agent indicated for PsA from January 1, 2002, until December 31, 2018, were identified and followed until medication stop date or the end of observation period. Patients were considered non-persistent whenever a permissible lag time of 6 months from the time of prescription issuance until medication filling date was exceeded. Treatment changes were based on physician decisions and patient preferences. Demographic data including age, sex, body mass index (BMI), ethnicity, smoking history, and socioeconomic status as well as Charlson comorbidity index were retrieved. Data regarding use of steroids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) were also extracted. Descriptive statistics, including means (standard deviations) for continuous variables and frequencies (%) for categorical variables, were used. Persistence estimates were derived using non-parametric survival analysis using Kaplan-Meier functions, with treatment discontinuations as failure events. Cox regression hazard ratio models were conducted to investigate factors associated with drug persistence. Results A total of 2301 PsA patients with 2958 treatment periods were identified and included in the analyses. Mean age of the study population was 50.9 ± 14 years, 54% were females, 70.4% were with BMI > 25, 40% were current smokers, and 76% were with a Charlson comorbidity index > 1. The most commonly prescribed drug was etanercept (33%), followed by adalimumab (29%), golimumab (12%), secukinumab (10%), ustekinumab (8%), and infliximab (8%). While approximately 40% of patients persisted on therapy following 20 months of treatment, only about 20% of patients remained on any particular biologic agent after 5 years. Analyzing the data for all treatment periods while taking into account all lines of therapy revealed that secukinumab had a higher persistency than adalimumab, infliximab, and ustekinumab, with a log rank of 0.022, 0.047, and 0.001, respectively. Female sex and smoking were associated with lower drug persistence (HR = 1.25, 95% CI = 1.13–1.38 and HR = 1.109, 95% CI = 1.01–1.21, respectively). On analyzing the data using only the first indicated biologic line, no superiority of any single anti-tumor necrosis factor-alpha (anti-TNFα) agent was observed, while secukinumab was found to be superior as second line therapy to adalimumab, etanercept, infliximab, and ustekinumab but not to golimumab with a log rank P value of 0.001, 0.004, 0.025, and 0.002, respectively. Conclusions In this large observational cohort studied in the era of biologic therapy, a relatively low drug persistence was observed, with female sex and smoking having a negative impact on persistency. None of the anti-TNFα agents was found to be more persistent than others as first line therapy, while secukinumab was found to be superior to other biologics when indicated as second line of therapy.

Background Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg–Strauss syndrome, is a rare multisystem disease characterized by asthma, rhinosinusitis, and eosinophilia. Cardiac involvement, present in half the patients, may be life threatening. Case summary A young woman with long-standing asthma and nasal polyposis was admitted with new-onset dyspnoea, sinus tachycardia, and eosinophilia. She had severe biventricular thrombosis and severe tricuspid regurgitation (TR) on echocardiography, with preserved ejection fraction of both ventricles. Cardiac magnetic resonance (CMR) imaging showed diffuse subendocardial late gadolinium enhancement (LGE). She had a positive test for perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) confirming the diagnosis of ANCA positive EGPA. She was treated with anticoagulation, high-dose corticosteroids, cyclophosphamide, and rituximab with gradual resolution of her symptoms. Follow-up echocardiography showed significant improvement in ventricular thrombi and TR but could not reliably exclude residual ventricular thrombus. Repeat CMR at 11 months confirmed complete resolution of both ventricular thrombi and near complete resolution of LGE. Discussion Cardiac involvement in EGPA, a rare cause of heart failure, can manifest as severe biventricular thrombosis and severe TR, resulting in heart failure with preserved ejection fraction. Combined immunosuppression and anticoagulation can lead to complete remission within a year. CMR is instrumental for both diagnosis and follow-up of EGPA, allowing for safe discontinuation of oral anticoagulation.

Objective To assess the attitudes and common practices of adult rheumatologists in the US regarding health care transition (HCT) for young adults with rheumatic diseases. Methods An anonymous online survey was sent to US adult rheumatologist members of the American College of Rheumatology to collect demographic data and information on attitudes and common practices regarding the transition process. Results Of 4,064 contacted rheumatologists, 203 (5%) completed the survey. Almost half of respondents (45.1%) were never trained in transition practices, and 74.7% were not familiar with the American Academy of Pediatrics/American Academy of Family Physicians/American College of Physicians Consensus Statement About Transitions for Youth with Special Healthcare Needs. Only 56.2% felt comfortable caring for former pediatric patients. The vast majority of respondents (90.7%) did not have a multidisciplinary transition team, and 37% did not have a plan for transitioning pediatric patients into their practice. Most adult rheumatologists were unsatisfied with the current transition process (92.9%), due to insufficient resources, personnel (91.1%), and time in clinic (86.9%). They also were unsatisfied with referral data received concerning previous treatments (48.9%), hospitalization history (48%), disease activity index (45.1%), medical history summary (43.9%), comorbidities (36.4%), medication list (34.1%), and disease classification (32.6%). Three major barriers to HCT were lack of insurance reimbursement (33.7%), knowledge about community resources (30.8%), and lapses in care between primary provider and specialist (27.8%). Conclusion This survey identified substantial gaps in knowledge and resources regarding HCT for young adults with rheumatic diseases. These may be best addressed by further training, research, dedicated resources, adequate payment, and practice guidelines.

Background: The treat-to-target approach was recently adopted for psoriatic arthritis (PsA) management. Objective: To assess the implementation of the “treat-to-target” (T2T) concept in daily management of PsA by use of composite scores of disease activity versus clinical judgement alone. Methods: A total of 117 PsA patients from a longitudinal PsA cohort were enrolled consecutively in the study during each patient’s first clinic visit during 2016–2017. Clinic notes from the treating rheumatologist were reviewed by an independent rheumatologist, noting clinical impression of disease activity, treatment changes based on clinical judgement, and rationale. Treatment changes were then compared to the use of formal disease activity parameters in Minimal Disease Activity (MDA) and Disease Activity Index for Psoriatic Arthritis (DAPSA) composite measures. All associations were assessed using the chi-square test or the Mann–Whitney test, as appropriate. Results: The 117 PsA patient cohort consisted of 65.5% women, mean age 58.4 ± 13.6 years. Clinical judgement of treating rheumatologist concorded with MDA and DAPSA in 76 (65.5%) and 74 (64.9%) patients, respectively. Agreement between clinical judgement and composite measure criteria did not correlate with patient age, sex, alcohol/tobacco use, or treatment regimens chosen. Disagreement between physician assessment and MDA occurred in 40 (34.5%) cases: in 30 cases, the MDA status was overestimated due to disregard of patient reported outcomes (PRO), while underestimation of MDA status occurred in 25% of cases with treatment changes made in patients with a single active joint or enthesis. Underestimation of disease activity using DAPSA occurred in 22 cases and could be attributed to disregarding tender joint count, patient pain visual analogue scale and C-reactive protein level. Conclusion: In our cohort, agreement between clinical impression and formal composite measure utilization for implementation of T2T strategy occurred in 65% of patients. Discordance resulted from physicians’ overlooking PRO and emphasizing objective findings when using clinical judgement alone.

Objectives As global vaccination campaigns against COVID-19 disease commence, vaccine safety needs to be closely assessed. The safety profile of mRNA-based vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) is unknown. The objective of this report is to raise awareness of reactivation of herpes zoster (HZ) following the BNT162b2 mRNA vaccination in patients with AIIRD. Methods The safety of the BNT162b2 mRNA vaccination was assessed in an observational study monitoring post-vaccination adverse effects in patients with AIIRD (n = 491) and controls (n = 99), conducted in two rheumatology departments in Israel. Results The prevalence of HZ was 1.2% (n = 6) in patients with AIIRD compared with none in controls. Six female patients aged 49 ± 11 years with stable AIIRD: RA (n = 4), Sjogren’s syndrome (n = 1), and undifferentiated connective disease (n = 1), developed the first in a lifetime event of HZ within a short time after the first vaccine dose in five cases and after the second vaccine dose in one case. In the majority of cases, HZ infection was mild, except a case of HZ ophthalmicus, without corneal involvement, in an RA patient treated with tofacitinib. There were no cases of disseminated HZ disease or postherpetic neuralgia. All but one patient received antiviral treatment with a resolution of HZ-related symptoms up to 6 weeks. Five patients completed the second vaccine dose without other adverse effects. Conclusion Epidemiologic studies on the safety of the mRNA-based COVID-19 vaccines in patients with AIIRD are needed to clarify the association between the BNT162b2 mRNA vaccination and reactivation of zoster.

OBJECTIVE: We aimed to assess the implementation of the treat-to-target (T2T) concept in rheumatoid arthritis (RA) patients in daily practice. METHODS: All RA patients visiting one of the 7 academic medical centers in Israel in June 2015 with at least 3 previous clinic visits were included in this study. A common questionnaire was used to collect data from patients’ medical records, and two independent rheumatologists evaluated the collected data for the implementation of the T2T concept. The associations between T2T implementation and the categorical and continuous variables were assessed. RESULTS: The study included 724 patients with a mean (standard deviation) age of 62.6 (13.97) years and 575 (80.4%) of them were women. Four centers used more than one scoring method, with Disease Activity Score-28 and Clinical Disease Activity Index) being most commonly used. Only 276 (38.1%) patients had disease score results in ≥3 visits, and the T2T recommendations were implemented for 245 (33.8%) of the 724 patients. The rate of implementation was higher in younger (p=0.028) rheumatoid factor-positive patients (p=0.011) and varied between centers (11.1%–87% p

To assess the prevalence of risk factors associated with cardiovascular disease (CVD) and CVD-related morbidity in a large Middle-Eastern psoriatic arthritis (PsA) cohort. A retrospective case control study was conducted using Israel’s largest health care provider’s patient database from 2000 to 2013. For each patient with PsA, 10 patients with no history of psoriasis or arthritis were matched for age and sex. Analysis of CVD-related risk factors and morbidity included hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus type 2 (DM-2), obesity, smoking, ischemic heart disease (IHD), congestive heart failure (CHF), cerebrovascular accident (CVA), carotid artery disease, peripheral vascular disease (PVD), aortic aneurism, valvular heart disease (VHD), and cardiomyopathy. Statistical analysis was conducted using t test and chi-square tests as appropriate. Univariate and multivariable logistic regression models assessed the association between PsA and CVD-related risk factors and morbidity. Three thousand one hundred sixty-one PsA patients were included, with average age 58 ± 15.0 years, of whom 53.4% were women. Increased prevalence of DM-2, HLD, HTN, and obesity (OR 1.7, 1.5, 1.5, 1.5 respectively) was noted in the PsA group. Increased prevalence of IHD (p

Background: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. Methods: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. Findings: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the MRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Atypical rheumatic manifestations included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. Interpretation: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. Funding: none.

Lupus myocarditis is a relatively rare manifestation of systemic lupus erythematosus. The majority of patients who experience myocardial involvement are females of young age. Here, we report a case of an 87-year-old male who was hospitalized because of perimyocarditis 2 weeks after undergoing percutaneous coronary intervention. Despite standard therapy his condition worsened, biomarkers and inflammation indices remained elevated, and pericardial effusion accumulated. The use of cardiac magnetic resonance (CMR) imaging, along with thorough history taking and testing for relevant antibodies allowed to establish the unusual diagnosis of lupus myocaridits. We demonstrate that lupus myocarditis may occur even in elderly males, as supported by characteristic CMR features.

Background Angiogenesis plays a central role in the pathophysiology of rheumatic diseases. Patients with psoriatic arthritis (PsA) demonstrate increased vascularity over patients with rheumatoid arthritis (RA), with unknown mechanisms. Methods We evaluated the serum levels of several pro- and anti-angiogenic factors in 62 PsA patients with active disease, 39 PsA patients in remission, 33 active RA patients, and 33 healthy controls (HC). Additionally, we used an in vitro co-culture system of fibroblast (HT1080) and monocytic-like (MM6) cell lines, to evaluate how their interactions affect the secretion of angiogenic factors and angiogenesis promoting abilities using scratch and tube formation assays. Results PsA patients, regardless of disease activity, exhibited higher levels of EMMPRIN/CD147, IL-17, and TNF-α relative to RA patients or HC. Factors, such as IL-6, and the ratio between CD147 and thrombospondin-1, exhibited elevated levels in active PsA patients relative to PsA patients in remission. Secretion of CD147, VEGF, and MMP-9 was increased in vitro. CD147 neutralization with an antibody reduced these levels and the ability of endothelial cells to form tube-like structures or participate in wound healing. Conclusions CD147 plays a role in mediating angiogenesis in PsA, and the therapeutic possibilities of neutralizing it merit further investigation.

Polymyalgia rheumatica (PMR) is one of the most common inflammatory rheumatologic condition occurring in older adults. It is characterized by proximal pain and stiffness in the shoulders, neck, and/or pelvic girdle in individuals over 50 years of age along with evidence of an intense systemic inflammatory response. Although the above clinical symptoms are very characteristic for the condition, it can be mimicked by other autoimmune, infectious, malignant, and endocrine disorders chief among which are giant cell arteritis (GCA) and elderly-onset rheumatoid arthritis (EORA). Recently, PMR was reported in relation to treatment with immune checkpoint inhibitors. Current treatment of PMR consists of low-to-medium doses of glucocorticosteroids (GC) with variable response rates and disease recurrence estimated to occur in 50% of patients while tapering down GC doses. In addition, GC-based regimens cause much of the morbidity associated with PMR in older adults, requiring close monitoring for GC-induced toxicity during therapy and highlighting the need for novel therapeutic strategies. Here, we review the latest findings in the field regarding specific etiologic factors, genetic associations, diagnostic methods, and advancements in treatment strategies and disease monitoring indices. Recent discoveries involving novel therapeutic targets in GCA have accelerated the study of PMR pathophysiology and have advanced treatment strategies in PMR management leading to current trials in IL-6 blocking agents. PMR remains an enigmatic inflammatory condition affecting older adults, with current treatment approach causing much morbidity in this patient population. Advancements in our understanding of novel immunopathologic targets can serve as a solid foundation for future treatment strategies in the field.

Objective.To assess the prevalence of systemic lupus erythematosus (SLE) in a psoriatic arthritis (PsA) cohort and to compare it to the general population using the database of a large healthcare provider.Methods.We analyzed the database of a PsA cohort (2002–2017), matched for age and sex, with randomly selected controls for demographics, clinical and laboratory manifestations, and dispensed medications. Statistical analysis used t test and chi-square test as appropriate. In the PsA group, incidence density sampling was performed matching PsA patients without SLE as controls to each case of PsA with SLE by age and follow-up time. Univariable and multivariable conditional logistic regression analyses were used to assess factors affecting SLE development.Results.The PsA and control groups consisted of 4836 and 24,180 subjects, respectively, with a median age of 56 ± 15 years, and of whom 53.8% were female. Eighteen patients (0.37%) in the PsA group and 36 patients (0.15%) in the control group were diagnosed with SLE (P = 0.001). SLE patients without PsA had higher anti-dsDNA and anticardiolipin antibodies. The usage of drugs with known potential to induce SLE was higher in the PsA than in the control group. Older age at PsA diagnosis, shorter PsA duration, and statin treatment were associated with SLE in PsA patients.Conclusion.A 2.3-fold increase in the prevalence of SLE in PsA relative to the control group was found. Risk factors for SLE development included older age at PsA diagnosis, shorter PsA duration, and statin treatment. The association between PsA and SLE may affect treatment choices and medication development.

The aims of this study were to evaluate the prevalence of metabolic syndrome (MetS) in psoriatic arthritis (PsA) patients according to the most recent definition in a Mediterranean population and to determine its association with biomarkers of inflammation and serum adipocytokine levels.Demographic, clinical, and laboratory data were collected on 74 patients with PsA and 82 control subjects. The presence of MetS was determined according to the current "harmonization" definition. Serum adipocytokines were analyzed. Continuous variables were compared by t test and discrete variables by χ test. Multivariate regression models compared the association between the presence of MetS and the blood levels of adipocytokines.The prevalence of MetS was higher in PsA patients compared with the control group: 54.8% versus 36.6%, respectively (P = 0.02; odds ratio, 2.33; 95% confidence interval, 1.16-4.69). The main difference between the 2 groups was waist circumference. No association was found between MetS and parameters of articular and skin disease activity or treatment. Leptin levels and leptin/adiponectin ratio were higher in PsA patients compared with control subjects: 83.4 versus 51.7 ng/mL (P = 0.001) and 6.3 × 10 versus 4.1 × 10 (P = 0.015), respectively. There was no significant difference in the adiponectin levels between the groups.The prevalence of MetS was higher in PsA patients compared with non-PsA control subjects in this Mediterranean population. Clinicians caring for PsA patients ought to be aware of the increased risk of MetS in PsA patients, confirmed in different regions worldwide. The increased MetS seems to be linked to central obesity in these patients, and appropriate treatment recommendations are advised.

Juvenile psoriatic arthritis (JPsA), a subtype of juvenile idiopathic arthritis (JIA), constitutes 5% of JIA. The literature is inconsistent regarding features of JPsA, and physicians debate whether it is a distinct entity within JIA. A biphasic age of onset distribution has been noted. Early-onset disease is characterized by female predominance, small joint involvement, dactylitis, and positive antinuclear antibodies. Late-onset JPsA resembles adult-onset psoriatic arthritis (PsA), with male predominance, psoriasis, enthesitis, and axial disease. Recent studies report improved outcomes, likely due to the widespread use of traditional and biologic disease-modifying antirheumatic drugs. Conflicting HLA associations have been reported in JPsA, but notably both HLA class I and II allele associations are suggested. Similar to PsA cohorts, subjects with JPsA have a lower frequency of a protective interleukin 23R allele than controls or other JIA subtypes. Data in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) patient registry suggest the aggressive characteristics of JPsA: 24.6% of children have joint damage 4.6 years after symptom onset. Pediatric and adult PsA classification criteria define different JPsA cohorts within the registry and support a previous suggestion that the International League of Associations for Rheumatology criteria for JPsA may be overly stringent. Increased collaboration between pediatric and adult physicians and comparative research on these clinically related conditions are warranted.

Objective.We aimed to estimate the proportion of underdiagnosis and undertreatment of cardiovascular risk factors (CVRF) in an international multicenter cohort of patients with psoriasis and psoriatic arthritis (PsA).Methods.A cross-sectional analysis was conducted of patients with psoriatic disease from the International Psoriasis and Arthritis Research Team cohort. The presence of modifiable CVRF [diabetes, hypertension (HTN), dyslipidemia, smoking, elevated body mass index, and central obesity] and the use of appropriate therapies for HTN and dyslipidemia were determined. The 10-year CV risk was calculated according to the Framingham Risk Score. Physician adherence with guidelines for the treatment of dyslipidemia and HTN was assessed. Regression analysis was used to assess predictors of undertreatment of HTN and dyslipidemia.Results.A total of 2254 patients (58.9% PsA, 41.1% psoriasis) from 8 centers in Canada, the United States, and Israel were included. Their mean age was 52 ± 13.8 years and 53% were men. Of the patients, 87.6% had at least 1 modifiable CVRF, 45.1% had HTN, 49.4% dyslipidemia, 13.3% diabetes, 75.3% were overweight or obese, 54.3% central obesity, and 17.3% were current smokers. We found 59.2% of patients with HTN and 65.6% of patients with dyslipidemia were undertreated. Undertreatment was associated with younger age (≤ 50 yrs), having psoriasis, and male sex.Conclusion.In real-world settings, a large proportion of patients with psoriasis and PsA were underdiagnosed and undertreated for HTN and dyslipidemia. Strategies to improve the management of CVRF in psoriatic patients are warranted.

Background:Anti-IL17 agents, such as Secukinumab (SEC) and Ixekizumab (IXE) have been shown to be efficacious for the treatment of psoriasis and PsA12. In the field of psoriasis, there is growing evidence of a successful switching between the two anti-IL-17 agents in case of an insufficient response to one of the treatments3 There is no information on the efficacy of switching between anti IL17 agents in PsA.Objectives:To assess the clinical response to IXE in patients with PsA following SEC failure.Methods:A retrospective observational study was conducted in two rheumatology centers in Israel, including PsA patients with a history of treatment with SEC, further treated with IXE for a minimum of 3 months. Lack of efficacy, loss of efficacy, and side effects over time were reported as a reason for switching to another anti-IL17 agent. The mean difference between the beginning of the follow up period and the different follow up points (6 and 12 months) was tested using a one-sample t-test. Time until treatment failure was estimated using Kaplan–Meier curves, and compared using the log-rank test. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using the Cox proportional-hazards model to test the association between each variable and the time to treatment failure.Results:The study included 23 PsA patients (11♀/12♂), mean age 58.7 years±13.4 SD. Most patients (n=20, 86%) received 2+ TNFi and 10 patients (43%) received both TNFi and ustekinumab. Median number of biologics prior to SEC was 3 (IQR 2-4). There was a significant improvement in TJC at 6 and 12 months (-2.16 [-4.0, -0.3]; p=0.025 and-1.69 [-3.09, -0.28]; p=0.022, respectively). SJC was significantly improved at 6 months but not at 12 months (-2.68 [-5.3, -0.04]; p= 0.046 and -1.50 [-4.25,1.25]; p=0.26, respectively). CDAI score was significantly improved at 6 months (-10.19, [-16.26, -4.1], p=0.002) and at 12 months (-9.29 [-14.8, -3.71], p=0.003) as was SDAI score (-10.13 [-16.4, -3.8], p=0.003 and -12.2 [-17.1, -7.2], p=0.0002). At six months, PASI50 was achieved by 81% (13 patients), PASI75 was achieved by 63% (10 patients), PASI90 was achieved by 50% (8 patients) and PASI100 by 31% (10 patients). At 12 months, PASI50 and PASI75 was achieved by 57% (8 patients), PASI90 was achieved by 43% (6 patients) and PASI100 by 21% (3 patients).Over time, of the 23 patients treated with IXE, 15 patients (65%) had experienced treatment failure, with a median treatment period of 8 months (IQR 6.5-13.5), of which 4 (17%) had primary treatment failure and 11 patients (48%) secondary treatment failure. Reasons for treatment cessation were: worsening psoriasis (4 patients (27%)), worsening peripheral arthritis (4 patients (27%)), both (7 patients (47%)), worsening of axial disease (2 patients (13%)) and adverse events (1 patient, 6%).Conclusion:patients after failure of multiple biologic treatments experienced significant response of peripheral arthritis and dermatologic disease on IXE after they had previously failed SEC. . However, in this refractory cohort of PsA, the effect was limited on time with 65% failure after a median time of 8 months.Within class switch from SEC to IXE is a plausible therapeutic option in PsA patients following secukinumab failure.References:[1]Mease PJ, McInnes IB, Kirkham B, et al. N Engl J Med. 2015;373(14):1329-1339.[2]Nash P, Kirkham B, Okada M, et al. Lancet Lond Engl. 2017;389(10086):2317-2327.[3]Bokor-Billmann T, Schäkel K. J Dermatol Treat. 2019;30(3):216-220Disclosure of Interests:None declared.

Objective.Adult patients with psoriatic arthritis are at increased risk for obesity and metabolic syndrome, but data regarding adiposity in children with juvenile psoriatic arthritis (JPsA) are limited. Our study assessed adiposity in children with JPsA in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry.Methods.Patients with JPsA in the CARRA registry were divided into nonoverweight and overweight groups using recommendations from the US Centers for Disease Control, and differences in demographic and clinical characteristics between groups at baseline and after 1-year followup were assessed using chi-square test, Fisher’s exact test, T test, or Mann-Whitney U test, as appropriate. The prevalence of overweight status in the JPsA registry patients was compared to rheumatoid factor–positive and −negative polyarticular juvenile idiopathic arthritis (RF+polyJIA; RF−polyJIA) registry cohorts and the US pediatric population, using a chi-square goodness-of-fit test.Results.Overweight children represented 36.3% of this JPsA cohort (n = 320). Compared to nonoverweight children, they were significantly older at symptom onset and rheumatologist’s first assessment, and scored significantly worse on patient/physician outcome measures. At 1-year followup, changes in body mass index were not associated with changes in clinical features or outcome measures. The prevalence of overweight and obesity in patients with JPsA was significantly higher than in RF+polyJIA patients, RF−polyJIA patients, and the US pediatric population.Conclusion.In this registry, almost 1 in 5 patients with JPsA were obese and more than one-third were overweight. This is significantly more than expected compared to the US pediatric population, and appropriate longterm followup of this JPsA subgroup is warranted.

Objective.To investigate endocrine comorbidities in patients with psoriatic arthritis (PsA).Methods.A retrospective, cross-sectional study was performed with the database of Clalit Health Services, the largest healthcare provider in Israel, between 2002 and 2014. Patients with PsA were identified and matched by age and sex to healthy controls. The following morbidities were analyzed: hypo/hyperthyroidism, hypo/hyperparathyroidism, hyperprolactinemia, Cushing disease, Addison disease, diabetes insipidus, diabetes mellitus (DM), pituitary adenoma, acromegaly, and osteoporosis. Descriptive statistics were applied. The associations between PsA and endocrine comorbidities were analyzed by univariable and multivariable analysis.Results.The study included 3161 patients with PsA, 53.4% women, mean age 58.4 ± 15.4 years, and 31,610 controls. Comparative analyses yielded higher proportion of hypothyroidism (12.7% vs 8.6%, p < 0.0001), Cushing disease (0.3% vs 0.1%, p < 0.0001), osteoporosis (13.2% vs 9.1%, p < 0.0001), and DM (27.9% vs 20.7%, p < 0.0001) in the PsA group compared with the control group. In the multivariable regression analysis, the following diseases were more frequent in the PsA group: hypothyroidism (OR 1.61, 95% CI 1.47–1.81), DM (OR 1.35, 95% CI 1.18–1.42), Cushing disease (OR 3.96, 95% CI 1.67–9.43), and osteoporosis (OR 1.56, 95% CI 1.37–1.78).Conclusion.PsA is associated with a high frequency of hypothyroidism, osteoporosis, DM, and Cushing disease. Awareness of these comorbidities may help physicians provide the optimal medical care to patients with PsA.

Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease. Dyslipidemia is a known adverse effect of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody used in RA treatment. We aimed to assess the effect of TCZ on lipid profile and adipokine levels in RA patients. Height, weight, disease activity scores, lipid profile and atherogenic indices (AI), leptin, adiponectin, resistin, interleukin-6, and high-sensitivity C-reactive protein (CRP) were measured before and four months after initiation of TCZ in 40 RA patients and 40 healthy controls. Following TCZ treatment, total cholesterol, high density lipoprotein (HDL), and triglycerides were significantly elevated, but no significant changes in weight, body mass index (BMI), low density lipoprotein (LDL), and AI were observed. Compared with controls, significantly higher adiponectin levels were measured in the RA group at baseline. Following TCZ treatment, resistin levels and the leptin-to-adiponectin ratio increased, adiponectin levels decreased, and leptin levels remained unchanged. No correlation was found between the change in adipokine serum levels and changes in the disease activity indices, nor the lipid profile. In conclusion, the changes observed suggest a protective role for TCZ on the metabolic and cardiovascular burden associated with RA, but does not provide a mechanistic explanation for this phenomenon.

Background Patients with psoriasis and psoriatic arthritis (PsA) can develop a variety of comorbidities including metabolic syndrome, diabetes, hypertension, cardiovascular diseases and depression. Comorbidities, in turn, may influence the therapeutic regimen and affect treatment results. Previous studies show a high incidence of coexistence of psoriasis and systemic lupus erythematosus (SLE). Unlike psoriasis, the coexistence of PsA and SLE has been reported only in case reports. Objectives To assess the prevalence of SLE in a PsA patient cohort and to compare it to the general population using the database of a large health care provider. Methods The study, which was conducted from 2002-2017, is a retrospective study on a PsA cohort consisting of 4,836 PsA patients matched for age and sex with 24,180 randomly selected control patients. Data on this cohort was derived from the database of more than 4.3 million people enrolled in the largest health care provider in Israel, Clalit Health Services. The database was used to extract demographic data, such as age, sex, ethnicity and socioeconomic status; clinical and laboratory manifestations of SLE; medication dispensed and SLE-inducing medications. T-test was used to compare continuous variables and a Chi-square test was used for categorical variables. All tests were 2-sided; p values of Results The PsA study group consisted of 4,836 subjects, at a median age of 56+/-15, 2603 (53.8%) of whom were females. The control group consisted of 24,180 subjects matched for age and sex. 18 patients (0.37%) in the PsA study group, and 39 patients (0.16%) in the control group where diagnosed with SLE (p=0.002). SLE patients without co-existing PsA had higher anti-double stranded DNA (anti-dsDNA) positivity (92.3% vs 66.7%, p=0.022) and positive anti-cardiolipin (ACL) antibodies (46.2% vs 16.7%, p=0.041). No other significant differences were observed between the two groups in terms of clinical and laboratory manifestations of SLE. PsA patients with concomitant SLE compare to PsA patients without SLE were more often female (100% vs 53.7%, p Conclusion A 2.3 fold increase in the prevalence of SLE in PsA patients than in the control group was found in our study population. There were no significant differences in the clinical and laboratory manifestations of SLE between these two groups. The positive correlates between SLE and PsA may point to common underlying pathogenetic pathways and may affect treatment choices and medication development. More research is needed for a better understanding of this diseases association. Disclosure of interests Danielle Korkus: None declared, Tal Gazitt: None declared, Ilan Feldhamer: None declared, Idit Lavi: None declared, amir Haddad: None declared, Erez Batat: None declared, Sari Greenberg-Dotan: None declared, arnon Cohen Grant/research support from: Prof. Arnon Cohen received research grants from Janssen, Novartis and abbVie and Sanofi, Consultant for: Prof. Arnon Cohen served as a consultant, advisor for abbVie; amgen; Boehringer ingelheim; Dexcel pharma; Janssen, Lilly; Neopharm; Novartis, Perrigo; Pfizer; Rafa; Sanofi, Speakers bureau: Prof. Arnon Cohen served as speaker for abbVie; amgen; Boehringer ingelheim; Dexcel pharma; Janssen, Lilly; Neopharm; Novartis, Perrigo; Pfizer; Rafa; Sanofi, Devy Zisman Grant/research support from: Dr D Zisman received research grants from Pfizer, Janssen, Consultant for: Dr D Zisman served as a consultant, for Pfizer, abbvie, Novartis, Ellie-Lilly, Sanofi, Speakers bureau: Dr D Zisman served as a speaker for abbVie, Janssen, Lilly, Novartis, Pfizer, Sanofi

Objective To assess the immunogenicity and safety of vaccination against seasonal influenza in psoriatic arthritis (PsA) patients treated with secukinumab versus healthy controls (HC). Methods PsA patients administered secukinumab for ≥3 months and HC received the Sanofi Pasteur vaccine composed of 3 antigens (H3N3, H1N1, and B) and underwent clinical and laboratory assessments on the day of vaccination and 4–6 weeks later. Immunogenicity of the vaccine was evaluated by hemagglutination inhibition assay against those 3 antigens. Responders to each antigen were defined by a 4-fold increase in the antigen titer or by seroconversion in patients whose baseline level was Results Thirty-two consecutive PsA patients treated with secukinumab for ≥3 months comprised the study group, 10 of whom received concomitant conventional synthetic disease-modifying drugs, mostly methotrexate. There were 17 age- and gender-matched HC (median age 48.5 years, 6 females). The geometric mean titers of each antigen increased significantly in both groups. The number of responders in each group was similar for H3N2 and H1N1, and significantly higher for B/Brisbane in the PsA group. The proportion of patients with a seroprotective level (a titer >1/40) was high and similar in both groups. There was no correlation between the response rate and age, gender, or selected parameters of disease activity (tender/swollen joint counts, Leeds enthesitis index, physician and patient global assessment, psoriasis area severity index, and C-reactive protein). No disease exacerbation was observed following the vaccination. No serious adverse effects were observed in both groups during the study period. Conclusion Secukinumab treatment does not affect the humoral response to influenza vaccine of patients with PsA.

Background:Psoriatic arthritis (PsA) is a chronic, immune-mediated, systemic inflammatory arthritis associated with comorbidities including metabolic syndrome, cardiovascular risk factors and cardiovascular disease (CVD).Objectives:To evaluate the prevalence of venous thromboembolism (VTE) in a PsA patient cohort using a large health care provider database.Methods:A large health care provider database serving 4.7 million healthcare subscribers was interrogated for an adult patient cohort who were newly diagnosed with PsA between January 2005 (start date) and 31 December 2018 with date of diagnosis considered the index date. A risk set was employed to randomly select 4 controls without PsA as a comparator group to the PsA cohort matched by age, sex, ethnic group, and index date. Both groups were followed from the index date until the first occurrence of VTE event, death, or end of follow-up 31 December 2019, whichever came first. Marginal model with robust covariant estimate counting for the matching was used to estimate the crude and adjusted hazard ratio (HR) for the association between PsA and VTE. Within the group of PSA patients, Cox proportional hazard regression models was used to calculate the risk of having VTE given demographic variables, SES, smoking, selected comorbidities, and conventional vs biologic disease modifying anti-rheumatic drugs (c/bDMARD). Continuous variables were summarized with mean ± standard deviation, and categorical variables were presented as numbers and proportions. All tests were 2-sided; p values of < = 0.05 were considered statistically significant. All data were analyzed using SPSS, 24 (IBM SPSS Statistics for Windows, version 24.0, 2016, Armonk, NY) and SAS, 9.4 (SAS institute Inc, Cary, NC).Results:The PsA cohort consisted of 5,275 patients, 53.2% females with mean age of 51.66 ±15.41. The control group consisted of 21,011 subjects matched for age and sex. In relation to the control group, the PsA cohort had a higher SES (25.1% vs 23.4%, p30, cancer, IHD, vascular disease, and previous VTE found to be associated with VTE in the PsA group relative to controls in both univariate and multivariate analyses. The higher prevalence of VTE in PsA patients relative to controls did not remain statistically significant in multivariate analysis following adjustment for risk factors. Within the PsA group, patients with VTE were more often of older age and with past history of VTE. Both cDMARD and bDMARD were not associated with increased risk of VTE among PsA patients.Conclusion:The prevalence of VTE was higher in PsA group compared to the general population, but after adjustment for comorbidities and risk factors, it no longer remained statistically significant. Among PsA patients, age and previous history of VTE were associated with increased risk of VTE. Addressing VTE risk in the management of patients with PsA is recommended especially in the era of Janus kinase inhibitors.Disclosure of Interests:None declared

Background:The epidemiology of COVID19 among patients with AIIRD may be influenced by a dysregulated immune system, immunosuppressive therapies and behavioral patterns. Data regarding the epidemiology of COVID19 among patients with AIIRD is scarce.Objectives:To assess the pattern of COVID19 pandemic among patients with AIIRD compared to the general population in IsraelMethods:At the beginning of the COVID-19 pandemic, we established a national registry of patients with AIIRD, diagnosed with COVID-19, based on voluntary reporting by the treating rheumatologist. All the members of the Israeli Society of Rheumatology were encouraged to participate and repeatedly reminded to report any new cases. Rheumatology centers from 11 hospitals from the Northern and Central part of Israel participated in this study. The registry included demographic data, AIIRD diagnosis and duration, systemic organ involvement, co-morbidities, treatment (conventional synthetic disease modifying drugs (csDMARDs), biologic/targeted (b/ts) DMARDs, corticosteroids use, dose and treatment duration, date of COVID19 diagnosis, severity of the viral disease and complications, duration of hospitalization, if required, treatment for COVID 19, laboratory results and outcome. The diagnosis of COVID 19 was made by a positive SARS CoV2 PCR. The indications for SARS CoV2 PCR testing in Israel comprise clinical symptoms or exposure to a confirmed close contact. Severe illness was defined by SpO2 30 breaths/min, PaO2/FiO2 50% on chest imaging.The epidemiological data regarding the number of COVID19 confirmed patients, the number of severe cases and the rate of mortality among the general population per day and per week, were extracted from the data dashboard of the Israeli Ministry of Health. We analyzed data from 02.2020 to 15.01.2021.Results:During the study period we experienced 3 waves of COVID 19 pandemic. The governmental management of COVID19 spread, at the beginning of the pandemic, included inforcement of severe travel restrictions and social distancing, followed eventually by a preventive lockdown, in spite of the relatively low number of cases. Easing of the restrictions, lifting the travel ban, opening of the commerce and schools led to 2 much more severe waves, which triggered 2 new lockdowns. Up to January 2021, 549763 Israelis had confirmed COVID19, 30% of whom had severe disease, 0.84% died (30% of the patients with severe disease).We identified 190 AIIRD patients (mean(SD) age 52(18), 30% males) who had confirmed COVID19. The weekly incidence curve of patients with rheumatic diseases correlated with the curve of the general population (Figure 1).Sixty-one % of the patients with AIIRD received csDMARDs, 41% were on b/tsDMARDs, 39% on chronic corticosteroids, 12% on ≥10mg prednisone. Forty-seven% of patients required hospitalization, 20% had severe COVID19. Sixteen patients (42% of patients with severe COVID19) (mean(SD), median age 64.7(15.4),67)) died (systemic sclerosis-4 patients, rheumatoid arthritis – 6, systemic lupus erythematosus – 2, antiphospholipid syndrome-2, granulomatous polyangiitis -1, polymyalgia rheumatica-1). The AIIRD was active in 56% of them, 50% received csDMARDs, none of them were on b/tsDMARDs, 31% received chronic prednisone>10 mg. All patients who died had at least 2 comorbidities.Conclusion:The pattern of spread of COVID19 in AIIRD patients is similar to the general population despite repeated mass media alerts for enhanced social distancing for elderly and immune suppressed patients. The disease tends to be more severe with enhanced mortality, especially in those with active AIIRD disease and organ involvement (lungs, heart, renal), older age and co-morbidities. A reporting bias cannot be excluded.Figure 1.Acknowledgements:Both first authors contributed equally to the manuscript.Disclosure of Interests:None declared.

Background:Diagnostic delay is a major challenge in axial spondyloarthritis (axSpA) with an extended interval of 8-10 years in Europe and 14 years in the United States between symptom onset and disease diagnosis (1, 2).Objectives:To assess the delay in the diagnosis of axSpA over time in a real world axSpA cohort diagnosed in the last 3 decades and to evaluate factors associated with this delay.Methods:A cohort of axSpA patients was recruited from a national multicenter registry of inflammatory arthritis. This cohorts’ demographic, clinical and diagnostic variables were studied. The diagnostic delay was defined as the time interval between the year of first symptom and year of diagnosis. The mean and median diagnostic delay were calculated. A survival analysis was performed evaluating the association between the demographic, clinical and diagnostic variables on the diagnostic delay.Results:Of the 373 axSpA patients in the registry, 198 (47%) are men. Ankylosing spondylitis fulfilling New York criteria was diagnosed in 73% of the patients. HLA-B*27 positivity was found in 64% of patients. The majority of the patients (63%) reported symptom onset between the age of 21-45, 21% before the age of 21 and 16% after the age of 45. Nine percent were diagnosed before the age of 21, 28% between 21-30, 23% between 31-40, 21% between 41-50 and 18% after the age of 50. One hundred and ten patients were diagnosed before 2000, 133 between 2001-2009 and 130 between 2010-2020. The mean and median delay in diagnosis was 9.1, 6 (±8.4) years when diagnosed before 2000, 5, 4 (±4.1) years when diagnosed 2001-2009, and 2, 1 (±1.5) years when diagnosed 2010-2020, respectively (graph 1). The only variable which was found to be associated with a shorter delay was the interval between symptom onset and first rheumatology consult: HR of 5.86 (4.3-8, pConclusion:Delay in axSpA diagnosis has significantly improved in this real-world cohort during the last decade. The most significant factor associated with a faster diagnosis was the time of the first rheumatology consult relative to symptom onset. Increasing the awareness of disease manifestations and early referral to a rheumatology service can improve the diagnosis delay of axSpA.References:[1]Sorensen J, Hetland ML, all departments of rheumatology in D. Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: results from the Danish nationwide DANBIO registry. Ann Rheum Dis. 2015;74(3):e12.[2]Deodhar A, Mittal M, Reilly P, Bao Y, Manthena S, Anderson J, et al. Ankylosing spondylitis diagnosis in US patients with back pain: identifying providers involved and factors associated with rheumatology referral delay. Clin Rheumatol. 2016;35(7):1769-76.Graph 1.The improvement in the delay in diagnosis of axial spondyloarthropathy over the last 3 decadesDisclosure of Interests:None declared.

Background:Secukinumab (Cosentyx) is a human IgG1 monoclonal antibody that selectively binds to and neutralizes IL-17A. Several prospective randomized control trials have demonstrated the efficacy and safety of secukinumab in PsA, but there is a paucity of real life data in the PsA population.Objectives:To prospectively study secukinumab’s safety, efficacy, and tolerability in the cohort of PsA patients from the Israeli registry of inflammatory diseases.Methods:PsA patients fulfilling the CASPAR criteria from the Israeli registry of inflammatory diseases were included in the analysis, from 2010 to November 2019. The primary end point was secukinumab drug survival compared to other available TNFi drug. Bivariate and multivariate analysis of the factors that affect the drug event free survival was done by cox regression analysis. Drug survival according to treatment line (all treatment lines, or 2ndand above treatment lines) was examined using Kaplan-Meier curves.Results:Four hundred and four PsA patients were included, which had 709 treatment episodes (initiations) during the study period. Ninety patients had been treated with secukinumab (22%). Secukinumab treated patients were significantly older at time of initiation of treatment, and disease duration was longer. Secukinumab was more likely to be a second, third or forth line of treatment than the TNFi. . Time to an inefficacy event was longer for secukinumab than any other anti-TNF treatment. As a first line treatment secukinumab had drug survival similar to other TNFi. As a second or third line treatment, secukinumab had a better drug survival than other TNFi. Methotrexate did not have a significant effect on inefficacy event rate in combination treatment with secukinumab. Secukinumab, as infliximab and golimumab, was as effective in the higher BMI group as it was in the normal weight to obese groups. Smokers (current or past) did better on secukinumab than on TNFi. Secukinumab had a similar rate of adverse events compared to TNFi.Conclusion:In this multicenter real world study, secukinumab had a comparable drug survival to TNFi. As a second and beyond line of treatment secukinumab had a better drug survival and lower HR for an inefficacy event. IL-17 inhibition is an effective mechanism of action to treat PsA in real life, and should be used more frequently as a first and second line treatment.Tables and a graph:Table 1.Inefficacy events according to treatment and drug survival in 1, 2, and 3 years.DrugTotal episodesInefficacy events (%)HR95% CIP value1styear survival %2ndyear survival %3rdyear survival %SEC9030 (33.3)10.095865841ETA20286 (42.6)1.160.77-1.760.479755850IFX8734 (39.1)1.010.62-1.650.966826452ADA227103 (45.4)1.360.9-2.040.143715346GOL103103 (50)1.641.05-2.590.031635042Table 2.inefficacy events and drug survival according to line of treatment.DrugTotal episodesInefficacy events (%)HR95% CIP value1styear survival %2ndyear survival %3rdyear survival %1stlineSEC132 (15.4)10.216929276ETA13055 (42.3)3.250.79-13.340.101765951IFX2811 (39.3)2.880.64-13.010.168816352ADA10337 (35.9)2.630.63-10.910.183796359GOL2514 (56)4.551.03-200.0456050402ndand 3rdlinesSEC347 (20.6)10.039906666ETA6829 (42.6)1.680.74-3.850.218735751IFX5120 (39.2)1.420.6-3.360.431856454ADA11962 (52.1)2.51.15-5.480.022654635GOL5223 (44.2)2.260.97-5.270.066550464thlineSEC4321 (48.8)10.082824424ETA42 (50)1.10.25-4.730.9026733–IFX83 (37.5)0.830.25-2.790.7626969–ADA54 (80)4.871.6-14.810.00530––GOL2613 (50)1.290.64-2.580.473625231Figure 1.Cumulative survival without an inefficacy event of secukinumab compared to TNFα inhibitors regardless of treatment line.Disclosure of Interests:Tali Eviatar: None declared, Devy Zisman Consultant of: Novartis, Merav Lidar Consultant of: Novartis, Tatyana Reitblat Consultant of: Novartis, Alexandra Balbir-Gurman Consultant of: Novartis, Ori Elkayam Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Novartis, Jansen

Background:Persistence in biologic therapy in psoriatic arthritis is critical to optimize symptom remission, functional capacity and health care costs.Objectives:To estimate the persistence to biologic treatment prescribed to PsA patients in a real-life setting as well as factors associated with improved biologic drug survival in these patients.Methods:Patients with PsA from a large health care provider database with at least two consecutive dispensed prescriptions of a biologic agent indicated for PsA from January 1st, 2002 until December 31st, 2018 were identified and followed until medication stop date or the end of observation period. Patients were considered non-persistent whenever a new prescription was dispensed and a permissible gap of 6 months was exceeded prior to starting on this biologic agent from the prescription date. Treatment changes were based on physician decisions and patient preferences.Demographic data including age, sex, BMI, ethnicity, smoking history and socioeconomic status as well as Charlson comorbidity index were retrieved. Data regarding use of steroids and non-biologic disease-modifying anti-rheumatic drugs were also extracted. Descriptive statistics, including means (standard deviations) for continuous variables and frequencies (%) for categorical variables, were used. Persistence estimates were derived using non-parametric survival analysis using Kaplan-Meier functions, with treatment discontinuations as failure events. Cox regression hazard ratio models were conducted to investigate factors associated with drug persistence.Results:2301 PsA patients with 2958 treatment periods were identified and included in the analyses. The mean age was 50.9±14 years of whom 54% were females, 70.4% of the study population had a BMI>25, and 36% were obese(BMI>30), 40% were current smokers, and 76% had a Charlson comorbidity index higher than 1. The most commonly prescribed drug was etanercept, followed by adalimumab, golimumab, secukinumab, ustekinumab and infliximab at 33%, 29%, 12%, 10%,8% and 8%, respectively. Only about 20% of patients remained on a particular biologic agent after 5 years, whereas about 40% persisted on therapy following 20 months of treatment. A Kaplan-Mayer survival analysis with pairwise comparisons of all treatment choices with respect to lines of therapy was conducted. When analyzing the data for all treatment periods and taking into account all lines of therapy, secukinumab had a higher persistency than adalimumab, infliximab and ustekinumab, with a Log Rank of 0.022, 0.047 and 0.001, respectively, as is shown in figure 1. Female sex and smoking were associated with lower drug persistence (HR=1.25, 95%CI 1.13-1.38 and HR=1.109, 95%CI 1.01-1.21, respectively). When analyzing the data regarding second-line biologic agents, secukinumab was found to be superior to adalimumab, etanercept, infliximab and ustekinumab but not to golimumab with a Log-Rank P value of 0.001, 0.004, 0.025 and 0.002, respectively (figure 2). On analyzing the data using only the first indicated biologic line, no superiority of any single anti-Tumor Necrosis Factor-alpha (anti-TNFα) agent was observed.Conclusion:In this large observational cohort, in the era of biologic therapy, a relatively low persistence was observed, with female sex and smoking having a negative impact on persistency. None of the anti-TNFα agents as first line therapy was found to be more persistent than others, while secukinumab was found to be superior to other biologics when indicated as second line of therapy.References:NoneFigure 1.Figure 2.Acknowledgments:noneDisclosure of Interests:None declared

Background Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease.1 Dyslipidemia is a known adverse reaction to tocilizumab (TCZ), the anti-interleukin-6 receptor antibody, used in RA treatment. Objectives To assess the effect of TCZ on lipid and adipokine levels in the serum of RA patients Methods Forty RA patients with active disease initiating TCZ treatment and 40 healthy matched controls were included. Height, weight, disease activity score (DAS28), lipid profile and atherogenic indices (AI) were measured before and four months after TCZ treatment initiation. Serum concentrations of leptin, adiponectin, resistin, interleukin-6 and high sensitivity CRP were measured by ELISA in both study groups. Statistical analysis: The differences in clinical and laboratory data of RA patients between baseline and follow up were assessed by paired t-test and by linear mixed models with repeated measures for adipokines levels after adjustment to BMI, statin treatment and disease duration. To compare the adipokines levels between RA and control groups adjusted to baseline BMI and statin treatment we used ANCOVA models. HsCRP and IL-6 were compared between the two groups by two-tailed Mann Whitney test. The results were considered statistically significant when p≤0.05. Results The average age of the study population was 57.5±11 years, 82.5% were women, with a disease duration of 8.7±5.6 years. The majority of the patients responded to TCZ and reduced their diseases activity from DAS28 score of 5.45±1.06 to 3.46±1.37 (p Conclusions The impact of TCZ treatment on lipid metabolism is complex. The elevation in HDL without change in AI, and the tendency toward normalisation of the adipokine profile observed, suggests a protective role of TCZ treatment against the cardiovascular burden in RA patients. Reference [1] Lago F, Gomez R, et al. Cardiometabolic comorbidities and rheumatic diseases: focus on the role of fat mass and adipokines. Arthritis Care Res2011; 63:1083–90. Disclosure of Interest None declared

Background Minimal disease activity (MDA) in psoriatic arthritis (PsA) is a composite outcome measure that represents the multifaceted domains of psoriatic disease including the joints, enthesis and skin, as well as patient‘s reported outcomes (PRO). MDA is currently used as a goal of treatment in the “treat-to-target” (T2T) approach in PsA management. 1 Objectives To assess the implementation of the T2T concept in PsA patients. Methods A retrospective analysis of all the patients included in a PsA registry during 2016- 2017 was performed. Medical charts were reviewed by an independent rheumatologist and the following data were collected: patient demographics, duration of PsA and psoriasis, alcohol and tobacco use, treatment changes, as well as items that constitute the MDA including the tender and swollen joint count, enthesitis, psoriasis area skin score (PASI), physician and patient evaluation of disease activity and pain and the health assessment questionnaire (HAQ) score. Medical records were reviewed to assess whether T2T concept was indeed followed by the treating rheumatologist to determinate whether MDA was achieved and medication changes were made. The associations between T2T concept implementation and categorical and continuous variables were assessed by Chi square test, or t-test as appropriate. The association between the physician’s assessment at each visit with each of the MDA parameters (active versus inactive) was assessed by Chi square test. Results The records of 117 consecutive patients were evaluated, one patient was excluded due to lack of data. The mean age was 58.4±13 years, of whom 76 (65.5%) were women. The T2T approach was implemented in 76 (65.5%) patients. There was no correlation between the T2T implementation and patient age, gender, alcohol and tobacco use, disease activity parameters at the patient‘s visit and the various treatment regimens. The physician assessment of disease activity did not correlate with the MDA score in 40 (34.5%) patients. In most cases 30 (75%), this discrepancy occurred because physicians labelled patients as having inactive disease while disregarding the PRO category of the MDA score, including 29 patients who reported a high VAS pain score, 22 patients reporting a high patient global disease activity and 25 patients reporting a high HAQ- score. In the other 10 (25%) of cases, the treating rheumatologists made treatment changes because they considered patients as having active disease based on one tender or swollen joint or enthesis, despite these patients actually meeting MDA criteria. Conclusions In our cohort, the T2T concept was implemented in 65.5% of the visits in accordance with other PsA studies. The main obstacle that we encountered in implementation of MDA concept was in physicians’ overlooking the PRO components of the score. Efforts are needed to increase the accurate use of the MDA score and treat to target concept in daily practice. Reference [1] Gossec L, McGonagle D, Korotaeva T, Lubrano E, de Miguel E, Ostergaard M, Behrens F. Minimal Disease Activity as a Treatment Target in Psoriatic Arthritis: A Review of the Literature. J Rheumatol2018Jan;45(1):6–13. Disclosure of Interest None declared

Objectives: Belimumab has recently been approved for the treatment of systemic lupus erythematosus (SLE) refractory to standard therapy. Following one case of an SLE flare after cessation of belimumab, we hypothesized that this might lead to a rebound phenomenon and possible exacerbation of SLE.Method: Members of the Israeli Society of Rheumatology were contacted by e-mail and asked to report cases of an SLE flare following cessation of belimumab treatment.Results: Three cases of SLE patients who experienced a severe SLE flare following cessation of belimumab therapy were reported. In all cases, belimumab was given as treatment for active mucocutaneous manifestations and/or polyarthritis with improvement in all three patients, one of whom achieved disease remission. In all three cases, patients experienced a severe flare in previously uninvolved major organ systems, including one case of class IV lupus nephritis accompanied by a new-onset severe headache with elevated cerebrospinal fluid (CSF) protein and...

Objectives To study the association between traditional disease-modifying antirheumatic drugs (c-DMARD) or anti-TNF-α agents and herpes zoster (HZ) in patients with psoriatic arthritis (PsA). Methods A retrospective cohort study was conducted in patients with PsA between 2002 and 2013. Patients were grouped as follows: no DMARDs (Group A); c-DMARDs (Group B); anti-TNF-α agents (Group C); anti-TNF-α agents in combination with c-DMARDs (Group D). Crude incidence rates (IR) were calculated as number of HZ episodes per 1000 patient-years. A Cox regression model was used to adjust for HZ risk factors (age, gender, steroid use, Charlson Comorbidity Index score, and previous treatment) in order to estimate their contribution to the risk of the first HZ event. Results The study included 3128 patients, mean age 50.26±14.54 years; 46.2% male. During a period of 20 096 person-years 182 HZ events were observed. The crude IR (95% CI) of HZ in the study population was 9.06 per 1000 patient-years, and in Groups A-D 7.36 (5.41 to 9.79), 9.21 (7.5 to 11.21), 8.64 (4.84 to 14.26), 17.86 (10.91 to 27.58), respectively. In a multivariate analysis, age (HR 1.01, 95% CI 1.00 to 1.02), treatment with steroids (HR 1.08, 95% CI 1.04 to 1.13), and a combination of anti-TNF-α agents and c-DMARDs (HR 2.37, 95% CI 1.32 to 4.22) were significantly associated with HZ events. Conclusions In our database, the risk of HZ was significantly increased with age, treatment with steroids, and combination of anti-TNF-α agents and c-DMARDs, but not with c-DMARDs or anti-TNF-α therapy alone. Time to HZ event was shorter in patients treated with anti -TNF-α agents.

Rituximab is a monoclonal antibody directed against the CD20 antigen on the surface of normal and malignant B lymphocytes. Its use in autoimmune conditions is rapidly expanding. Late-onset neutropenia (LON) is a well-recognized side effect of rituximab therapy in lymphoma patients. Only a small number of cases of LON have been reported in patients with autoimmune disorders. The aim of this work is to review cases in Israel and to compare them to published cases in the literature thus adding to the body of knowledge regarding this unusual phenomenon. Members of the Israeli Rheumatology Association were encountered by e-mail, requesting reports of cases of LON after therapy with rituximab. Submitted cases were reviewed, with demographics and clinical data collated and tabled. Current cases were compared to previously published rheumatology cases. Twelve episodes of LON following rituximab therapy were reported. All patients were female with an average age of 50 years (range 22-78). LON occurred at an average of 155 days after therapy (range 71-330). The average leukocyte count was 1,456 white cells, with an average of 413 neutrophils (range 0-1,170 neutrophils). Three of the patients underwent bone marrow biopsies which showed white cell line maturation arrest with an increased number of lymphocytes. No blasts were seen. Our results add support to the growing evidence that this adverse event usually follows a benign course and is not an absolute contraindication for repeat treatment if required in the future. However, vigilance is recommended with routine periodic blood counts, especially 5 months following rituximab administration when the risk is expected to be the highest.

Comorbidities associated with psoriatic arthritis (PsA) include cardiovascular diseases, diabetes mellitus, and obesity. This study evaluated the association between PsA and common gastrointestinal (GI) diseases. A retrospective study was performed in Israel’s largest health care provider database between 2002 and 2013. 3161 PsA patients were matched for age and sex with 31610 randomly selected patients. We searched these patients’ records for the presence of peptic ulcer disease (PUD), reflux esophagitis, Crohn’s disease, ulcerative colitis, irritable bowel syndrome (IBS) and celiac disease. T-test was used to compare continuous variables and a Chi-square test was used for categorical variables. Multivariate logistic regression models were used to assess the association between PsA and GI comorbidities. PsA was associated with Crohn’s disease (OR 2.4, 95 %CI: 1.75–3.32, p

Objective.To assess the association between treatment with anti-tumor necrosis factor-α (TNF-α) agents and the occurrence of hospitalizations, their causes and complications, compared to treatment with traditional disease-modifying antirheumatic drugs in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS).Methods.A retrospective cohort study was conducted of patients with RA, AS, and PsA treated with anti-TNF-α agents between April 2002 and December 2007. Patients were assessed during the period of anti-TNF-α treatment (Group B) and compared to an equivalent period before initiation of anti-TNF-α therapy (Group A). All hospitalization charts were reviewed and diagnoses, comorbidities, concomitant medications, and clinical course were analyzed. Statistical analysis was performed using multivariate mixed Poisson regression.Results.In the study period of 57 months, 735 hospitalization events of 327 patients were analyzed. Statistically significant decreases were seen in the total number of hospitalization events as well as hospitalizations due to exacerbation of rheumatic diseases in Group B compared to Group A (44.4 vs 74.2 and 21.9 vs 47.5 per 100 patient-years, respectively; p < 0.0001). More infectious events (7.4 in Group B compared to 4.6 per 100 patient-years in Group A; p = 0.043) were associated with anti-TNF-α treatment, older age, and underlying disease, because patients with RA had higher rates of infections compared to patients with PsA and patients with AS.Conclusion.The overall effect of anti-TNF-α therapy was a significant decline in total hospitalization events. The decrease was more prominent in patients with RA than in patients with AS and patients with PsA, and reflected the significant decrease in hospitalizations due to rheumatic disease exacerbation. The decrease was more pronounced than the observed increase in infectious events.

Disease patterns and manifestations may vary among different populations and change over time. The purpose of our study was to define the demographic, clinical, roentgenologic, and laboratory findings in a recent cohort of psoriatic arthritis patients followed up in rheumatology clinics in northern Israel. We conducted a cross-sectional study of 149 psoriatic arthritis patients. Demographic, clinical, laboratory, and radiological data, with emphasis on the pattern of arthritis, treatment regimens, and co-morbidities were obtained from patient interviews and rheumatology file reviews. The mean age of our patients was 58.2, with a female preponderance (57.3%). Skin involvement preceded the arthritis or was diagnosed simultaneously in 90.1% of cases. The most common joint involvement was an RA-like arthritis (49.7% of the patients) correlating positively with age, female gender, and disease duration. Dactylitis and nail involvement were observed in 33.6 and 36.2% of the patients, respectively. Radiographic bone erosions were noted in a third of the patients, correlating with DIP and RA-like arthritis patterns. Most patients were treated with methotrexate (73.8%) and a combination therapy (41.4%). An increased incidence of hypertension, hyperlipidemia, and diabetes mellitus was noted in our cohort compared to the general Israeli population. Our survey, the first of its kind conducted in Israel, noted a relative increase in the polyarticular manifestation of PsA and a decrease in spondyloarthropathy, compared to historic series, with more aggressive disease found in women above the age of sixty. These findings are in line with recent surveys.

Only a limited number of patients with amyloidosis and pulmonary hypertension have been reported in the literature. We report a 73-year-old female with AL type amyloidosis who developed respiratory insufficiency and right heart failure because of severe pulmonary hypertension. There were no signs of cardiac involvement with amyloid or findings consistent with interstitial lung disease. Previous reports of pulmonary hypertension without an apparent parenchymal lung or myocardial involvement with amyloidosis are summarized. Pulmonary hypertension due to deposition of amyloid in the pulmonary vasculature is an uncommon finding; however, it should be considered in cases of unexplained pulmonary hypertension in patients with amyloidosis.

Drug survival has recently become an important clinical issue in psoriasis. However, there has been little research into factors associated with drug survival of methotrexate and acitretin. The aim of this study was to investigate factors associated with drug survival of methotrexate and acitretin treatment for psoriasis. Survival analysis was performed in patients who received methotrexate or acitretin for the treatment of psoriasis, drawn from the Clalit Health Services database. Investigated factors included demographic variables, obesity, metabolic syndrome, psoriatic arthritis, administration route and folic acid supplementation. Among 6,256 patients, factors associated with treatment drop-out were: younger age (p

Importance The risk for herpes zoster (HZ) in patients with psoriasis treated with biologic medications or other systemic treatments has been given little attention to date. Objective To describe the risk for HZ in patients with psoriasis and its relation to treatment. Design, Setting, and Participants A cohort study was performed using the administrative database of Clalit Health Services, the largest public health care provider organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. We extracted information for all patients who received a psoriasis diagnosis from January 2002 to June 2013. Follow-up was conducted until the end of July 2013. The study included 95 941 patients with psoriasis in the analysis, with 522 616 person-years of follow-up. Incidence of HZ events was calculated for each systemic antipsoriatic medication provided, during a follow-up period of 11 years and 7 months. We used a generalized estimating equation Poisson regression model to examine the effect of each systemic treatment for psoriasis on HZ incidence, adjusting for age, sex, psoriasis severity, Charlson comorbidity index, steroid treatment, and socioeconomic status. Main Outcomes and Measures Incidence of HZ associated with systemic therapies. Results In a multivariate analysis, it was observed that treatment with phototherapy (rate ratio [RR], 1.09 [95% CI, 0.62-1.93]; P = .99), methotrexate (RR, 0.98 [95% CI, 0.78-1.23]; P = .83), cyclosporine (RR, 1.16 [95% CI, 0.48-2.80]; P = .49), and biologic medications as a single agent (RR, 2.67 [95% CI, 0.69-10.3]; P = .14) was not associated with HZ. The use of combination treatment with biologic medications and methotrexate was significantly associated with an increased incidence of HZ (RR, 1.66 [95% CI, 1.08-2.57]; P = .02). The use of acitritin was associated with decreased incidence of HZ (RR, 0.69 [95% CI, 0.49-0.97]; P = .004). Conclusions and Relevance Physicians may need to consider offering an HZ preventive vaccine to patients receiving combination treatment with biologic medications and methotrexate, particularly if they have additional risk factors for HZ.

Epidemiological studies have shown that patients with psoriatic arthritis (PsA) are often affected by numerous comorbidities that carry significant morbidity and mortality. Reported comorbidities include diabetes mellitus, obesity, metabolic syndrome, cardiovascular diseases, osteoporosis, inflammatory bowel disease, autoimmune eye disease, non-alcoholic fatty liver disease, depression, and fibromyalgia. All health care providers for patients with PsA should recognize and monitor those comorbidities, as well as understand their effect on patient management to ensure an optimal clinical outcome.

Objective.The longterm use of tumor necrosis factor (TNF)-α blockers is limited by the formation of neutralizing antibodies. To the best of our knowledge, immunogenicity in psoriatic arthritis (PsA) has not been investigated in depth. Our objective was to evaluate the prevalence and significance of TNF-α blocker immunogenicity in PsA.Methods.Consecutive patients with PsA treated with either infliximab (IFX), adalimumab (ADA), or etanercept (ETN) > 3 months participated in our cross-sectional study. Their demographic and clinical characteristics, skin and joint disease activity, and records of use of methotrexate (MTX) and other medications were collected. Drug levels (ELISA) and antidrug antibodies (ADAb; Bridging ELISA) were evaluated before the next injection or infusion.Results.A total of 93 patients with PsA were recruited (48 receiving ADA, 24 IFX, and 21 ETN), with a mean age of 53 years (range 21–83 yrs), composed of 53% women. One-fourth of the patients were concomitantly treated with MTX. Altogether, 77% of the patients demonstrated therapeutic drug levels. High levels of ADAb were found in 29% of patients taking ADA, 21% taking IFX, and 0% taking ETN. ADAb significantly correlated with lower drug levels, higher 28-joint Disease Activity Scores, and higher global assessments. MTX use correlated significantly with a lower prevalence of ADAb.Conclusion.Significant levels of ADAb were present in up to 29% of patients with PsA treated with ADA or IFX. ADAb clearly correlated with low therapeutic drug levels and higher disease activity variables. The use of MTX significantly decreased ADAb prevalence, and its use should be strongly considered in combination with TNF-α blocker antibodies in patients with PsA.

Objective: To assess changes in macrophage phenotype and function after rituximab-induced B cell depletion in patients with rheumatoid arthritis (RA). Methods: 10 patients with RA were treated with rituximab, achieving significant B cell depletion 4 months later. Clinical improvement, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, mRNA of B cell activating factor (BAFF), interleukin (IL) 10 and CD86 in human monocyte-derived macrophages (HMDMs) and tumour necrosis factor α (TNFα) secretion from cultured HMDMs were assessed at baseline and after the depletion. Results: A clinical response of American College of Rheumatology (ACR) 50% improvement was noted in six patients, and another two patients responded with moderate improvement, equivalent to ACR 20–50% improvements. RF and anti-CCP antibodies were positive at baseline in seven of ten patients. RF disappeared or declined in six patients 4 months after treatment, correlating with clinical improvement. By contrast, anti-CCP remained unchanged in six patients. After rituximab treatment, and in association with clinical improvement, BAFF, IL10 and CD86 mRNA expression in HMDM were significantly upregulated compared with values at baseline. A significant decrease in TNFα in the supernatant of cultured HMDM was also noted. Conclusions: In addition to B cell depletion and attenuation in some of the specific autoantibodies, clinical improvement in rituximab-treated patients with RA occurred in association with changes in macrophage function.

A cohort of patients with recently diagnosed axial spondyloarthritis (SpA) was characterized with emphasis on gender differences and factors leading to delay in diagnosis. Clinical, laboratory, and imaging data of 151 consecutive patients diagnosed with ankylosing spondylitis or undifferentiated SpA in 2004–2009 and satisfying the new ASAS classification criteria for axial SpA, was collected and analyzed. Seventy-nine men and 72 women were enrolled. Both groups (men and women) had similar age of onset of disease-related symptoms, as well as similar delay time to diagnosis, follow-up duration and frequency of anti-TNF treatment. Inflammatory back pain, as a first symptom related to SpA, was reported more often by men, while women had more pelvic, heel, and widespread pain (WP) during the course of the disease. At the time of diagnosis, men were more limited in chest expansion and showed increased occiput-to-wall distance compared to women. Elevated erythrocyte sedimentation rate and/or C-reactive protein were detected in a similar proportion of men and women. Presence of WP in women almost doubled the delay in the diagnosis of SpA. No other differences in disease presentation or burden were demonstrated to correlate with delay in diagnosis.

Kikuchi Fujimoto disease (KFD) is a rare, benign disorder, usually characterized by cervical lymphadenopathy. Most available data on KFD has come from the Far East. We examined the characteristics of KFD in Israel.A retrospective analysis of the records of all patients diagnosed as KFD in seven medical centers in Israel and all the cases previously reported as having occurred in Israel in the literature.Nineteen patients were included, 13 new cases and six from the literature. Mean age of patients was 23 (range 9-50) years. Female/male ratio was 1.1:1. Cervical lymphadenopathy, the hallmark of KFD in the Far East (97%), was less frequent in Israel (44%). However, Israeli patients presented more often with generalized (26%) or retroperitoneal (21%) lymphadenopathy (P0.01). Systemic signs such as fever (73%), night sweats (21%), weight loss (21%), hepatomegaly or splenomegaly (25%), and elevated sedimentation rate (52%) were more common in Israeli patients compared to most reports from other parts of the world, excluding Germany (P0.05). Leukopenia was evident in most Israeli patients (72%) in contrast to other countries (P0.01). Clinical presentation of KFD in Germany was comparable to Israel in most aspects.The clinical presentation of KFD in Israel often resembles a systemic disease with fever, leukopenia and generalized or retroperitoneal lymphadenopathy in more than half of the cases, contrary to the presentation in the Far East, which typically includes cervical lymphadenitis, and less frequently, systemic manifestations.

ObjectiveWe assessed cardiac conduction properties in patients with psoriatic arthritis (PsA).MethodsElectrocardiogram (ECG) scans of 92 patients with PsA were compared to 92 age and sex matched nonpsoriatic, nonarthritic patients from general practice serving as controls.ResultsPR interval was found to be significantly longer in the PsA group compared to controls, 159.6 ± 21 ms versus 151.3 ± 26 ms, respectively (p = 0.021). No statistical difference was found with respect to the QRS interval or other atrial or ventricular conduction disturbances studied. No correlation was found between the PR interval and disease duration or PsA subtype. The use of non-steroidal antiinflammatory drugs did not affect the PR interval. Methotrexate was not found to influence the PR interval, compared to other disease modifying antirheumatic drugs. Two PsA patients (2.1%) had a PR interval > 0.2 ms. Their prolonged PR interval could not be explained by medication use. The abnormal prolongation of the PR interval was asymptomatic, requiring no additional intervention. No patient had complete heart block.ConclusionOur study may suggest subtle involvement of the atrioventricular node in patients with PsA.

Behcet's disease (BD) is known to vary in severity and manifestations in different populations.In an attempt to sort out genetic and environmental influences on disease expression, we carried out a study to assess the clinical features of BD in the adult Druze and Arab populations in north Israel, comparing 2 disparate ethnic groups of similar genetic background inhabiting the same geographic region.We compared 23 Druze and 30 Arab patients with BD. All patients fulfilled the classification criteria of the International Study Group for BD.Manifestations were similar in 2 groups. The most frequent BD manifestations among the Druzes were recurrent oral aphthae (100%) and genital aphthae (61%) versus 100% and 53% in Arab patients, followed by inflammatory ocular involvement, 65% versus 53%, respectively. Arthritis was noted in 39% of Druze, with 27% in Arabs. Anterior uveitis occurred in 9 Druze patients (48%) and panuveitis in 4, with no case of blindness when compared with 30% with anterior uveitis, 4 with panuveitis, and 4 cases of blindness (P0.04) among the Arabs. One Druze BD patient had deep vein thrombosis versus 8 Arab patients (P0.017). No pulmonary embolism, aortic aneurysm, nor valvular involvement was documented in the Druze versus 1 case of each in Arabs. No case of neuro-Behcet was reported in Druzes versus 6 cases of neuro-Behcet among Arabs (P0.023). The severity score was 4.0 (SD, 1.2) in Druze and 5.8 (SD, 1.9) in Arabs (P = 0.0004). The prevalence of HLA B51 did not differ significantly between the groups.Druze BD patients in Israel have a milder disease than do Arabs, similar to observations in familial Mediterranean fever. Druze BD patients had significantly less severe ocular disease and neurologic manifestations. Our results suggest an ethnic influence on expression of BD not related to HLA B 51.

Background Dysregulated expression levels of different microRNAs are reported in both serum and inflamed joints of RA patients. Objectives To determine whether administration of Tocalizumab (TCZ), a neutralizing anti-IL-6 receptor antibody, changes expression levels of selected miRNAs, which were previously described in the context of RA. Methods 40 RA patients diagnosed with moderate to severe disease activity according to both DAS28 and CDAI scores, and were started on TCZ therapy, were enrolled in the study. Serum samples that were obtained before treatment and 4 months after TCZ treatment initiation, were analyzed for the relative expression of miR-16, -21, -132, -146a, -150, -155, -203, -221, and -323 by qPCR. Results No significant changes in the expression levels of the tested miRNAs were found after TCZ treatment. However, when patients were stratified to responders and non-responders according to both the CDAI and DAS28 scores, the levels of miR-203 alone, out of the 9 miRNAs examined, were increased by 8.2% (p Conclusions The expression levels of miR-203 could serve as a potential biomarker that predicts a positive response to TCZ treatment in RA patients. References O9Connell, R. M., Rao, D. S., Baltimore, D. (2012) microRNA regulation of inflammatory responses. Annu Rev Immunol 30, 295-312. Fu, L., Jin, L., Yan, L., Shi, J., Wang, H., Zhou, B., Wu, X. (2014) Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility. Hum Immunol Sep 2014. Bottini, N. and Firestein, G. S. (2013) Epigenetics in rheumatoid arthritis: a primer for rheumatologists. Curr Rheumatol Rep 15, 372. Duroux-Richard, I., Jorgensen, C., Apparailly, F. (2012) What do microRNAs mean for rheumatoid arthritis? Arthritis Rheum 64, 11-20. Murata, K., Yoshitomi, H., Tanida, S., Ishikawa, M., Nishitani, K., Ito, H., Nakamura, T. (2010) Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis research & therapy 12, R86. Stanczyk, J., Ospelt, C., Karouzakis, E., Filer, A., Raza, K., Kolling, C., Gay, R., Buckley, C. D., Tak, P. P., Gay, S., Kyburz, D. (2011) Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation. Arthritis Rheum 63, 373-81. Acknowledgements The first and second authors are equal contributors. Disclosure of Interest None declared

Background: It is relatively difficult in a community setting to perform salivary gland biopsy or reliable diagnostic tests for salivary gland involvement in a patient suspected to suffer from Sjogren’s syndrome (SS). Objective: To investigate whether anti-Ro/La antibodies are a good substitute for salivary gland biopsy in community patients suspected to suffer from SS. Methods: Forty-one patients suspected as having SS due to dry eyes and mouth, articular complaints, and/or serological findings were examined for the presence of anti-Ro/La, and underwent minor salivary gland biopsy. Results: Sixteen patients (39%) were classified as primary SS by the American–European Consensus Group criteria. Twelve subjects had anti-Ro/La antibodies and 11 subjects in this group had positive biopsy findings. Of 29 patients without anti-Ro/La antibodies, only four manifested positive biopsy findings. A significant association was found between the presence of anti-Ro/La antibodies and positive salivary gland findings characteristic for SS (p

Background Psoriatic arthritis (PsA) is associated with higher prevalence and risk for cardiovascular morbidities [1,2]. Objectives The aim of the study is to substantiate these findings in our population and to examine additional aspects of cardiovascular morbidities, including congestive heart failure and cardiomyopathy. Methods A retrospective, longitudinal, cohort case control study was performed on records of patients with PsA between 2000 and 2013 from the database of Israel9s largest health care provider, Clalit Health Services. For each patient with PsA, 5 control patients without history of psoriasis or rheumatoid arthritis were chosen, matched for age and gender. The following morbidities were analyzed: ischemic heart disease (IHD), valvular heart disease excluding mitral valve prolapse, congestive heart failure (CHF), cardiomyopathy, idiopathic hypertrophic subaortic stenosis (IHSS), cerebrovascular accident (CVA), carotid artery disease, peripheral vascular disease (PVD), and aortic aneurism. T-test was used to compare continuous variables and Chi square test was used for categorical variables. Age, gender, socioeconomic status and ethnicity were entered into a multivariate regression model. Results The study included 3161 patients with PsA, 1474 males (46.6%) and 1687 (53.4%) females with a mean age of 58.29±15.44 years, and 15,805 controls. Comparative analysis demonstrated higher prevalence of the following in the case cohort: IHD (18.95% vs. 14.49%) p Conclusions A high prevalence of cardiovascular co-morbidities was found in this cohort of PsA patients. The spectrum of cardiac involvement was not limited to IHD, carotid artery disease and PVD, and included also increased risk of CHF, cardiomiopathies and valvular heart disease. A high index of suspicion, and close monitoring and treatment of cardiovascular risk factors are recommended. References Husni ME, Mease PJ. Managing comorbid disease in patients with psoriatic arthritis. Curr Rheumatol Rep 2010;12:281–287. Horreau C, Pouplard C, Brenaut E, Barnetche T, Misery L, Cribier B, et a l. Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review. J Eur Acad Dermatol Venereol 2013;27(Suppl. 3):12–29. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3830