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ObjectivesTo evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls.MethodsA prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2 IgG titre at 2–6 weeks (AIIRD n=720, controls n=122) and 6 months (AIIRD n=628, controls n=116) after the second vaccine, and 2–6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). T-cell immune response to the third vaccine was evaluated in a small sample.ResultsThe two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, pConclusionsThe two-dose BNTb262 regimen was associated with similar clinical efficacy and similar waning of the humoral response over 6 months among patients with AIIRD and controls. The third vaccine dose restored the humoral response in all of the controls and the majority of patients.

Tofacitinib is an approved treatment for rheumatoid arthritis (RA), but data on its use in the "real-world" are limited. We sought to analyse tofacitinib drug survival in the Israeli registry and compare it to other biologic agents.We included RA patients treated with tofacitinib, etanercept, golimumab, tocilizumab, or abatacept between 2010-2019. The primary endpoint was event-free survival (EFS), defined as the time from treatment initiation to a treatment failure event from any cause (i.e., inefficacy or intolerability). EFS was compared between agents using Cox regression and Kaplan-Meier analysis, stratifying patients by treatment line.A total of 964 eligible treatment courses were included (tocilizumab [325], etanercept [284], abatacept [127], tofacitinib [139], and golimumab [109]). In a univariate analysis, EFS with tofacitinib in the complete cohort was similar to etanercept, golimumab, and abatacept but was lower than tocilizumab) 3-year EFS 43% vs. 53%, HR 0.65). In a multivariable analysis, tofacitinib was similar to all other drugs, except for etanercept, which was inferior (HR 1.70); advanced treatment line was also associated with greater risk for failure (HR 1.64). In a univariable analysis stratified by the treatment line, tofacitinib had similar or better drug survival than other agents in the first and second lines. In the third line and beyond, tocilizumab had a higher EFS compared to tofacitinib (HR 0.57).Drug survival with tofacitinib is related to treatment line. Early introduction is associated with similar or better survival than other agents, whereas tocilizumab was superior in the third line or later.

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.

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.

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 Although the risk of cardiovascular disease has been discussed extensively in both psoriasis (PsO) and psoriatic arthritis (PsA), very few studies have addressed the occurrence of venous thromboembolic (VTE) events among PsO patients, and even fewer in PsA. Thus, our goal was to assess the association between PsA and VTE events using a large population-based database. Methods This retrospective cohort study includes all 5,275 patients with newly diagnosed PsA from the largest health care provider in Israel between January 2003 and December 2018. Identified PsA patients were matched by age, sex, ethnicity, and index date with 21,011 controls without PsA from the same database. Both groups were followed through June 30, 2019 for the occurrence of VTE event. Cox proportional hazard regression models were used to assess the association between PsA and VTE. Results PsA cohort consisted of 53.2% females with mean age of 51.7±15.4 Sixty-two patients (1.2%) were diagnosed with VTE in the PsA group and 176 patients (0.8%) in the control group (p=0.023, HR=1.40, 95% CI 1.05-1.87). However, there was no increased risk of VTE among PsA patients on multivariable analysis (p=0.16, HR=1.27, 95% CI 0.91-1.80). Within the PsA group, patients with VTE were more often of older age and with history of VTE. Conclusions This study suggests that the increased risk of VTE in PsA patients appears to be related to the underlying comorbidities and not independently associated with PsA. Age and previous history of VTE were the only risk factors associated with increased risk of VTE in patients with PsA. Addressing VTE risk is recommended especially in the era of Janus kinase inhibitors.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis, affecting up to 40% of patients with psoriasis. Constitutive expression by CD4+ T cells of an active form of STAT3, a signal transducer and transcription factor, has been shown to induce many of the major features of PsA in an animal model. We used high dimensional mass cytometry (CyTOF) to probe ex-vivo levels of phosphorylated STAT3 (pSTAT3) in circulating immune cell subpopulations from PsA patients during active and inactive states. We evaluated the frequency of 16 immune cell populations and the levels of the activated forms of STAT3 (pSTAT3) and, for comparison, STAT1 (pSTAT1) and Src (pSrc) in whole blood fixed shortly after collection. In addition to PsA patients, we studied active rheumatoid arthritis (RA) patients. Increased levels of pSTAT3 were found in all the CD4+ T cell subsets analyzed, specifically, Th1, Th2, Th17, T follicular helper (Tfh) and T regulatory (Treg) as well as in CD14+CD16- (classical) monocytes from active PsA patients compared to inactive patients. After correcting for body mass index (BMI), smoking and conventional disease modifying antirheumatic drugs (c-DMARDs), levels of pSTAT3 levels remained increased in Th1 and Tfh CD4+ T cells, and in CD14+CD16- monocytes from active patients compared to inactive patients. No differences between the patient groups were observed for pSTAT1 or pSrc. No differences were found between the active PsA and active RA groups after correction for multiple testing. During active PsA, circulating Th1 and Tfh CD4+ T cells, and CD14+CD16- monocytes expressing high levels of pSTAT3 may play a role in PsA pathophysiology, perhaps by migration to inflamed sites.

BackgroundAngiogenesis is a major contributor to the development of inflammation during Rheumatoid arthritis (RA), as the vascularization of the pannus provides nutrients and oxygen for the infiltrating immune cells and proliferating synoviocytes. Tocilizumab (TCZ) is an anti-IL-6 receptor antibody that is used in the treatment of RA patients, and has been shown to exert anti-inflammatory effects. However, its effects on angiogenesis are not fully elucidated, and the molecular mechanisms regulating this effect are unknown.MethodsWe evaluated the concentrations of several pro- and anti-angiogenic factors and the expression levels of several microRNA molecules that are associated with RA and angiogenesis in serum samples obtained from 40 RA patients, before and 4 months after the initiation of TCZ treatment. Additionally, we used an in vitro co-culture system of fibroblasts (the HT1080 cell line) and monocytes (the U937 cell line) to explore the mechanisms of TCZ action.ResultsSerum samples from RA patients treated with TCZ exhibited reduced circulating levels of EMMPRIN/CD147, enhanced expression of circulating miR-146a-5p and miR-150-5p, and reduced the angiogenic potential as was manifested by the lower number of tube-like structures that were formed by EaHy926 endothelial cell line. In vitro, the accumulation in the supernatants of the pro-angiogenic factors EMMPRIN, VEGF and MMP-9 was increased by co-culturing the HT1080 fibroblasts and the U937 monocytes, while the accumulation of the anti-angiogenic factor thrombospondin-1 (Tsp-1) and the expression levels of miR-146a-5p were reduced. Transfection of HT1080 cells with the miR-146a-5p mimic, decreased the accumulation of EMMPRIN, VEGF and MMP-9. When we neutralized EMMPRIN with a blocking antibody, the supernatants derived from these co-cultures displayed reduced migration, proliferation and tube formation in the functional assays.ConclusionsOur findings implicate miR-146a-5p in the regulation of EMMPRIN and propose that TCZ affects angiogenesis through its effects on EMMPRIN and miR-146a-5p.

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.

Calcinosis or dystrophic soft-tissue calcification occurs in damaged/devitalized tissues in the presence of normal calcium/phosphorus metabolism.1 It is a known complication of connective tissues diseases, especially juvenile dermatomyositis and systemic sclerosis (SSc), and may be localized or widespread.2 Previous data from the Scleroderma Clinical Trials Consortium showed calcinosis to be most commonly associated with digital ulceration, osteoporosis, telangiectasias, and acroosteolysis,3 as well as with anticentromere, anti-PM/Scl, and anticardiolipin antibodies.3 …

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

IntroductionVaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.MethodsA multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2–6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose.ResultsFollowing vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, pConclusionmRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.

To prospectively study real-world efficacy and safety of secukinumab in psoriatic arthritis (PsA) patients from the Israeli registry of inflammatory diseases.PsA patients fulfilling the CASPAR criteria were included in the analysis from 2010 to 2019. The primary endpoint was secukinumab drug retention compared to other TNF-α inhibitors (TNFi). Bivariate and multivariate analyses were made by Cox regression analysis. Drug retention according to treatment line was examined with Kaplan-Meier curves.Included were 404 PsA patients who had 709 treatment courses during the study period. Ninety patients had been treated with secukinumab (22%). The secukinumab-treated patients were significantly older and their disease duration was longer. Secukinumab was less likely to be the first line of treatment compared to TNFi. Secukinumab had a drug retention comparable to TNFi, and a better drug retention than TNFi among biologic-experienced patients. Neither methotrexate combination nor body mass index affected the inefficacy event rate. Secukinumab had a similar rate of adverse events as TNFi.This multicentre real-world study demonstrated that secukinumab had a drug retention comparable to TNFi. Secukinumab had a better drug retention than TNFi among biologic-experienced patients. IL-17 inhibition is an effective mechanism of action to treat PsA in real life.

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.

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.

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.

Objective.To evaluate the effect of pregnancy on disease activity in psoriatic arthritis (PsA).Methods.This is a retrospective case series. Review of the medical files of all female patients followed at the PsA clinic of 2 medical centers identified those with at least 1 pregnancy during followup and 1 visit during or soon after pregnancy.Results.Twenty-five women with PsA (out of 107 women of reproductive age followed up in our PsA clinics) and 35 pregnancies were enrolled. Thirty-three pregnancies resulted in live healthy babies. In the whole group, there was no significant change in disease activity throughout pregnancy, while in 16 (48%) of pregnancies, patients worsened during the first postpartum year. In 15 out of 21 pregnancies, in which the women had been treated before conception with biologics, treatment was discontinued close to pregnancy or during the first trimester. Five of those 15 patients had been classified as having mild to severe PsA activity prior to pregnancy. That number increased to 8, 9, and 14 during the first and second trimesters and postpartum period, respectively. There was no significant change in degree of disease activity in 6 patients whose biologics were continued beyond the first trimester. Improvement in disease activity was observed during pregnancy among the nonbiologics-treated patients. Corticosteroids were initiated or the dosage was increased during 6 pregnancies, all involving patients whose biologics were stopped before pregnancy.Conclusion.Continuation of biologics therapy was associated with a low level of disease activity and a low probability of flare during pregnancy. Stopping treatment with biologics before pregnancy is associated with flare during pregnancy and the postpartum period.

Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients.To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs.In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment.The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data.Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported.

Background There is limited information on the epidemiology of psoriatic arthritis (PsA) in general and in Middle Eastern populations in particular. The aims of this study were to estimate the prevalence and incidence rates of PsA and their temporal trends in the general population in Israel. Methods In this study, a cohort of adult patients with PsA was derived from the database of Clalit Health Services (CHS), Israel’s largest health fund, with over 4.4 million members. The crude and age- and sex-standardized prevalence and incidence rates of PsA from 2006 to 2015 in the general population were calculated. The variation in PsA prevalence was assessed in relation to several demographic factors. Results Among the 2,931,199 individuals aged 18 years and older registered in the CHS database in 2015, 4490 patients had a diagnosis of PsA (322 incident cases), resulting in overall crude prevalence and incidence rates of 0.153% (95% CI 0.149%, 0.158%) and 10.9 (95% CI 9.8, 12.3) per 100,000 population, respectively. The reported prevalence of PsA in Israel has doubled between 2006 and 2015 (from 0.073% to 0.153%). In contrast, the global incidence rate remained stable, with a gradual increase in incidence among individuals aged 51 to 70 years. PsA is associated with Jewish ethnicity, high socioeconomic status, and higher body mass index. Conclusions The prevalence and incidence of PsA in Israel are within the range of previous estimates from Southern European populations. An increase in the reported prevalence of PsA was observed over the past decade in the general population in Israel.

Cardiovascular (CV) morbidity and mortality is elevated in rheumatoid arthritis (RA), psoriatic arthritis (PSA) and ankylosing spondylitis (AS) patients. The inflammation not only accelerates atherosclerosis, but also influences CV risk factors such as lipid profile, blood pressure and insulin resistance. RA and PSA patients are initially treated with DMARDS (disease modifying anti-rheumatic drugs). However, if remission is not achieved in RA, a variety of biologics (anti- TNF rituximab, tocilizumab, abatacept) are added to the treatment regimen. In PSA, only anti-TNF drugs are approved. AS is treated solely by NSAIDS and anti-TNF drugs. DMARDS were found to reduce the CV morbidity in RA patients, in addition to their anti-inflammatory affect. However, it has not been proven that anti-inflammatory therapy reduces the cardiovascular risk in PSA and AS patients. Anti-TNF drugs have been shown to reduce CV morbidity and mortality in RA and AS patients, however their effect on these patient's lipid profile in not yet clear. Despite the scarce evidence available, it seems that rituximab may have a positive influence on the patient's lipid profile. Even though tocilizumab adversely affects the lipid profile, this drug's overall CV effect is still being examined in clinical trials. There is not enough evidence to determine the effect of abatacept on the lipid profile. These issues are currently in the focus of many clinical trials and no doubt these issues will be clarified in the future.

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.

To assess the fetal outcomes of pregnancies of systemic lupus erythrematosus (SLE) patients in northern Israel.A retrospective cohort study was conducted. The association between demographic characteristics, disease-related variables and adverse pregnancy outcome was assessed.Data were collected regarding 59 pregnancies of 35 SLE patients; 77.1% were Jewish patients and 22.8% Arab. None of the patients suffered from a major organ flare during pregnancy. There was no difference in the frequency of the different lupus manifestations across the two ethnic groups. The mean birth week of all pregnancies followed was 31.8 weeks. An adverse pregnancy outcome had occurred in 35.6% of the pregnancies. Intrauterine growth restriction was observed in 13.5% of the pregnancies. Antiphospholipid antibodies (APLA) positivity, past major organ involvement and a younger age at conception were associated with an adverse pregnancy outcome; however, ethnicity was not associated.The pregnancy outcomes of our cohort are similar to those previously published, worse than the general population. Ethnicity did not affect the fetal outcome.

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.

Behcet's disease (BD) has a higher prevalence in countries along the ancient silk route, but the actual prevalence in Israel is unknown. We evaluated the occurrence and clinical expression of BD in the northern region of Israel: in the whole population and by ethnic groups. The sample included all adult patients with BD (International Study Group criteria) treated at three medical centers in northern Israel. Patient data were collected by file review and physician survey. Relevant demographic data for the population served by the medical centers were obtained from the official Israeli authorities. A total of 112 patients were identified. The overall prevalence of BD was 15.2/100,000 and was similar in men and women. The prevalence rates among the Jewish, Arab, and Druze populations were 8.6, 26.2, and 146.4 per 100,000, respectively. Age at disease onset was similar in all ethnic groups and significantly lower in males (28.6+/-9.7 vs 32.9+/-11.3, p=0.03). There were no differences in disease manifestations by sex or ethnicity. All Druze patients were HLA-B5 positive, compared to 80.8% of the Arab patients and 72.0% of the Jewish patients. Recurrent oral ulcers in family members were more common in Arab patients (p=0.004). The BD severity index was significantly lower in Druze patients (p=0.05), mainly in males (p=0.03). This study confirms the high prevalence of BD in Israel and the variability in disease rates and expression by ethnic origin. Our findings, particularly regarding the Druze population, call for further field surveys and genetic studies.

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.

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis that can lead to decreased health-related quality of life and permanent joint damage leading to functional decline. In addition to joint and skin manifestations, both psoriasis and PsA are associated with numerous comorbidities and extraarticular/cutaneous manifestations, which may influence the physician’s choice of therapy. The objectives of this review are (1) to identify comorbidities in patients with PsA based on the available evidence; (2) to examine the effects of these comorbidities or extraarticular/cutaneous manifestation on the management of patients with PsA as well as the selection of therapy; and (3) to highlight research needs around comorbidities and treatment paradigms. This review is part of a treatment recommendations update initiated by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

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.

Seronegative spondyloarthritis (SpA) represents a group of diseases that share certain genetic, clinical, and radiographic features. Enthesitis, inflammation at the site of tendon insertion into the bone, involving both the axial and the peripheral joints, is an important sign of SpA. Clinical diagnosis of enthesitis, however, is neither sensitive nor specific; thus, the diagnosis of enthesitis often relies on typical abnormalities in imaging studies. Due to its low costs and availability, ultrasound is emerging as the preferred technique for detection of enthesitis for both clinical and research purposes. Ultrasonographic features of enthesitis include tendon hypoechogenicity and thickening, calcifications, bone erosions, and Doppler signal. Several semi-quantitative scoring systems have been developed to quantify ultrasonographic abnormalities of the entheses. These methods have been used for early diagnosis and classification of SpA as well as for monitoring response to treatment.

Objective. Vitamin D insufficiency appears to be a pandemic problem and is more common in inhabitants of high latitude compared to low latitude areas. We aimed to determine the prevalence of vitamin D deficiency/insufficiency in patients with psoriatic arthritis (PsA), its seasonal and geographic variation, and the possible association with demographics and disease activity.Methods. This study was conducted in a northern geographic area and in a subtropical region from March 2009 to August 2009. Most subjects were assessed in both winter and summer. Demographics, clinical data, skin photo type, and serum 25-hydroxyvitamin D (25[OH]D) levels were determined. Multivariate linear and logistic mixed models were used to assess the relationship with serum 25(OH)D levels.Results. In total, 302 PsA patients were enrolled. Two hundred fifty-eight patients were evaluated during the winter,while 214 patients were evaluated during the summer. 25(OH)D levels in winter and summer were adequate (north: 41.3%winter and 41.4% summer, south: 42.1% winter and 35.1% summer), insufficient (north: 55.7% winter and 58.6% summer,south: 50.9% winter and 62.2% summer), and deficient (north: 3% winter and 0% summer, south: 7% winter and 2.7%summer) among patients. There was no association between 25(OH)D levels, geographic and seasonal interaction, race,employment status, and skin photo type or disease activity in both seasons. No association between disease activity in summer and vitamin D levels in winter could be found.Conclusion. A high prevalence of vitamin D insufficiency among PsA patients was found. There was no seasonal variation in 25(OH)D levels among PsA patients in the southern and northern sites. No association could be established between disease activity and vitamin D level.

To assess the efficacy and safety of the influenza virus vaccine in systemic sclerosis (SSc) patients compared to healthy controls.Twenty-six SSc patients and 16 healthy controls were vaccinated with a trivalent influenza subunit vaccine (H1N1 A/Brisbane/59/2007(TGA 2008/81B) (H1N1), H3N2 A/Uruguay/716/2007 (A/Brisbane/10/2007-like, NIBSC8/124) (H3N2) and B B/Brisbane/60/2008 (TGA 2009/82/B) (B)). The subjects were evaluated on the day of vaccination and 6 weeks later. Disease activity was assessed by the Rodnan score, number of ulcers, number of tender and swollen joints, the presence of dyspnea, cough, dyspepsia and dysphagia, and patient (PDAI) and physician (PHDAI) disease activity evaluation by the visual activity score (VAS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. The humoral response was evaluated by haemagglutination inhibition (HI).At baseline, 62%, 15% and 88% of the SSc patients had protective levels against H1N1, H3N2 and B, respectively, versus 56%, 62% and 87% for controls. Six weeks later, the proportion of responders to H1N1 was significantly higher in the SSc patients (73%) compared to controls (37.5%) (p=0.0225). The proportion of responders to H3N2 and B was similar in both groups, and both had a significant increase in geometric mean titers for each antigen. A lower response to H1N1 was associated with interstitial lung disease, while patients on combination calcium channel blockers and iloprost therapy showed significantly better response to H1N1 and B antigens. Most underlying disease activity parameters remained unchanged.The influenza virus vaccine was safe and generated a satisfactory humoral response in SSc patients.

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.