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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.

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.

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 …

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

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.

Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA.To evaluate SC tocilizumab in a real-life clinical setting.Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed.Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively.The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.

Background/Purpose A universally accepted definition of axial psoriatic arthritis (axPsA) is lacking. We aimed to 1) assess the presence of axial involvement as defined by “at least unilateral grade 2 sacroiliitis (Uni2SI)” and 2) assess the radiographic progression of Uni2SI and identify risk factors for progression. Methods PsA patients participating in a prospective observational cohort were classified according to their highest sacroiliitis grade. The baseline features of patients with Uni2SI were compared to patients meeting the radiographic criteria of the modified New York Ankylosing Spondylitis (mNY AS) criteria. Risk factors were examined for progression from Uni2SI in a sub-group of patients with >1 follow-up radiographs. Logistic regression and a survival analysis were carried out and identified risk factors associated with radiographic mNY AS compared to Uni2SI. Results Axial disease defined as ≥Uni2SI was detected in 612/1354 patients (45%). mNY AS sacroiliitis was observed in 477 patients (35%). Radiographic progression of Uni2SI was assessed in 154 patients, 80 (52%) progressed to mNY AS criteria within 5.5 years. At baseline, progressors were diagnosed at a younger age (35.6 vs. 38.9, p = 0.05), had less degenerative disc disease (OR = 0.47, p = 0.02), worse peripheral radiographic damage (OR=1.02, p = 0.03) and worse psoriasis (OR = 1.09, p = 0.01) compared to non-progressors. Patients with an elevated erythrocyte sedimentation rate were more likely to progress (HR = 1.83, p = 0.02), while patients with longer disease duration were less likely to progress (HR = 0.95, p = 0.02). Conclusion The radiographic mNY AS criteria appear to be suitable for defining axial PsA according to radiographs. MRI definitions are needed as well for the most appropriate definition of axial PsA.

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 Mood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL-6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients. Materials and methods Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety, respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4 weeks and study completion. Results Ultimately, 91 patients were included in the study. The mean age was 54 years, and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters, respectively; HAQ-DI (r = .4, .42), DAS28 (r = .29, .32) and CDAI (0.28 and 0.33), all of them were statistically significant (P Conclusions This study has demonstrated a favourable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA.

ObjectiveTo describe the prevalence of inflammatory and structural lesions using whole spine MRI in patients with psoriatic disease, and to assess their correlation with clinical features and with axial spondyloarthritis (axSpA) classification criteria.MethodsThis retrospective analysis included patients with whole spine and sacroiliac joints (SIJ) MRI, selected from 2 populations: (1) active psoriatic arthritis (PsA), irrespective of axial symptoms; (2) psoriasis with confirmed or suspected PsA and axSpA symptoms. MRI spondylitis and/or sacroiliitis (MRI-SpA) was defined according to Assessment of Spondyloarthritis International Society (ASAS) consensus and by radiologist impression. Agreement between MRI-SpA and different inflammatory back pain (IBP) definitions (Berlin/ASAS/rheumatologist criteria) and the axSpA classification criteria were calculated considering MRI as gold standard. Logistic regression determined MRI-SpA-associated factors.Results93 patients were analysed (69.9% PsA; 30.1% psoriasis). Back pain was present in 81.7%, defined as IBP in 36.6%–57%. MRI-SpA was found in 9.7% of patients by ASAS definition and in 12.9% by radiologist impression, of which 25% had isolated spondylitis.Low agreement was found between the three IBP definitions and MRI-SpA. Rheumatologist criteria was the most sensitive (50%–55.6%) while ASAS and Berlin criteria were the most specific (61.9%–63%). axSpA criteria had poor sensitivity for MRI-SpA (22.2%–25%). Late onset of back pain or asymptomatic patients accounted for most cases with MRI-SpA not meeting axSpA or IBP criteria. Male sex was associated with MRI-SpA (OR 6.91; 95% CI 1.42 to 33.59) in multivariable regression analysis.ConclusionPrevalence of MRI-defined axSpA was low and showed poor agreement with IBP and axSpA criteria.

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.

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.

Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease that has 5 disease domains: peripheral arthritis, axial disease, dactylitis, enthesitis, and skin and nail disease1. Only 2–5% of patients with PsA have isolated axial disease; most patients with axial arthritis also have peripheral arthritis2,3,4. The prevalence of axial disease in patients with PsA varies with disease duration, occurring in 25–70% of patients with longstanding PsA3 and in 5–28% of patients with early disease5,6,7,8,9,10,11. These differences suggest that axial disease typically develops at a later stage in the disease course. In the Toronto PsA cohort, 15% of patients with PsA who did not have axial involvement at baseline developed axial PsA during 10 years of followup4. The risk factors for the development of axial disease early in the disease course were presence of HLA-B27, the presence of radiographic damage to peripheral joints, and an increased erythrocyte sedimentation rate (ESR), whereas the risk factors for developing axial involvement later on in the disease course were the presence of nail dystrophy, a high number of radiographically damaged joints, the presence of periostitis, and an increased ESR. Additionally, a family history of PsA reduced axial disease risk early in the disease course4. This study4 highlights the fact that different patients are likely to develop axial disease at different timepoints in their PsA disease course. This poses a significant limitation in studies with a cross-sectional design that identify patients at a single timepoint in their disease course compared to longitudinal studies that can record the changing course of the disease … Address correspondence to Dr. D.D. Gladman, Toronto Western Hospital, University Health Network, 399 Bathurst St., 1E410B, Toronto, Ontario M5T 2S8, Canada. E-mail: dafna.gladman{at}utoronto.ca

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 The aim of this study was to compare patients with ankylosing spondylitis with psoriasis (ASP) and without psoriasis (AS), to axial PsA (axPsA) patients. Methods Two adult cohorts were recruited from the AS clinic: ASP and AS. These two cohorts were compared with two adult cohorts recruited from the PsA clinic: axPsA (radiographic sacroiliitis: ⩾bilateral grade 2 or unilateral grade 3 or 4); and Peripheral PsA. All patients were followed prospectively according to the same protocol. The demographic, clinical and radiographic variables were compared. Adjusted means were used to account for varying intervals between visits. A logistic regression was performed and adjusted for follow-up duration. Results There were 477 axPsA patients, 826 peripheral PsA, 675 AS and 91 ASP patients included. AS patients were younger (P < 0.001), more male and HLA-B*27 positive (76%, 72% vs 64%, P ⩽ 0.001, 82%, 75%, vs 19%, P = 0.001). They had more back pain at presentation (90%, 92% vs 19%, P = 0.001), worse axial disease activity scores (bath ankylosing spondylitis disease activity index: 4.1, 3.9 vs 3.5 P = 0.017), worse back metrology (bath ankylosing spondylitis metrology index: 2.9, 2.2 vs 1.8, P < 0.001), worse physician global assessments (2.4, 2.2 vs 2.1, P < 0.001), were treated more with biologics (29%, 21% vs 7%, P = 0.001) and had a higher grade of sacroiliitis (90%, 84% vs 51%, P < 0.001). Similar differences were detected in the comparison of ASP to axPsA and in a regression model. Conclusion AS patients, with or without psoriasis, seem to be different demographically, genetically, clinically and radiographically from axPsA patients. axPsA seems to be a distinct entity.

Background:Angiogenesis is an important contributor to the development of Rheumatoid arthritis (RA). Tocilizumab (TCZ), an anti-IL-6 receptor antibody, is an immunosuppressant used in the treatment of RA patients, but its effects on angiogenesis and the molecular mechanisms regulating new blood vessel formation are not fully elucidated.Objectives:To evaluate the concentrations of pro- and anti-angiogenic factors in serum samples of RA patients, before and after the initiation of TCZ treatment and to explore in an in vitro co-culture system the mechanisms of TCZ action.Methods:We evaluated the concentrations of EMMPRIN, VEGF, MMP-9, IL-6, NGAL, endostatin and thrombospondin-1 (Tsp-1) using commercial ELISA kits from 40 RA patients, before and 4 months after the initiation of TCZ treatment. The levels of secreted EMMPRIN, VEGF MMP-9 and Tsp-1 were measured in an in vitro co-culture system of HT1080 fibroblasts and U937 monocytes with and without addition of anti-EMMPRIN blocking antibody. In the tube formation assay serum samples and supernatnats from the co-cultures were added to endothelial layer. Images were obtained after 6 hours of incubation and the number of closed lumens were counted in two separate fields. In the wound assay, supernatants from the co-cultures, with or without the addition of the anti-EMMPRIN antibody were added to the endothelial layer after scratching. The scratch site area was measured immediately and compared to the area after 24 hours of incubation to assess the distance of cell migration.Results:Study population included 40 RA patients, 33 (82.5%) females, mean age of 57.5±11.1 years, disease duration of 7.7±5.6 years, and 53.9% positive for rheumatoid factor initiating treatment with TCZ. In this patient cohort, 25/40 (62.5%) patients were classified as “responders” according to EULAR criteria.Following 4 mounts of treatment, statistically significant reductions in the levels of EMMPRIN/CD147 (p=0.035), without significant changes in serum levels of MMP-9, VEGF, MMP-3 and MMP-7 and of the anti-angiogenetic factors Tsp-1 and endostatin were found. A statistically significant decrease in the ratio between the pro-angiogenic factor EMMPRIN and the anti-angiogenic factor Tsp-1 that was calculated for each patient 4 months after initiating TCZ was found(p=0.031). The decrease in angiogenesis was manifested by the reduced number of closed lumen tube-like structures formed by EaHy926 endothelial cell line after incubation with serum samples 4 months after initiation of TCZ, relative to the number of closed lumens formed prior to TCZ initiation (p=0.007). The ratio between EMMPRIN and Tsp-1 was significantly reduced in the responding patients versus non-responders (p=0.033), while the levels of VEGF, MMP-9, Tsp-1, and EMMPRIN were unchanged.In vitro, the accumulation of the pro-angiogenic factors EMMRPIN, VEGF and MMP-9 in the supernatants was increased in the co-culture, while the accumulation of the anti-angiogenic factor Tsp-1 was decreased. When EMMPRIN was neutralized with a blocking antibody, supernatants derived from these co-cultures exhibited reduced migration, proliferation, and tube-like structure formation in functional assays.Conclusion:Our findings suggest an important role for EMMPRIN in mediating pro-angiogenic signals in RA patients, with EMMPRIN/Tsp-1 ratio serving as a marker of angiogenesis in RA. When administered to RA patients, TCZ in turn, exerts an anti-angiogenic effect through its regulation of EMMRPIN/CD147 levels.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: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

Ankylosing spondylitis (AS) was first identified in the late 17th century. 250 years later, inflammatory spine disease was recognized to be one of the patterns of psoriatic arthritis (PsA). Isolated spondylitis is rare among patients with PsA, occurring in less than 5% of patients; however, many patients with PsA have axial disease that is concurrent with peripheral arthritis. At the other end of the spondyloarthritis spectrum, psoriasis is observed in 10% of patients with AS. Although axial involvement in PsA can be indistinguishable from axial disease in AS, it can also differ in several respects, raising the question of whether axial PsA and AS (with or without psoriasis) are different clinical presentations of the same disease, or whether they are separate diseases that have overlapping features. In this Review, the clinical presentation, metrology, radiographic characteristics, genetic factors, treatment options and axial prognosis of the two diseases are addressed. The aim of this Review is to capture all available comparisons made to date, to highlight the similarities and differences between AS and axial PsA and to propose a research agenda.

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.

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.

The assessment of disease activity and flare and differentiating them from permanent damage in patients with SLE is challenging. The SLEDAI, SLEDAI-2K and SELENA-SLEDAI measure global disease activity. The BILAG measures organ-specific activity. The BILAG better captures the change in the different organs at the expense of complexity. The SRI is a composite index incorporating both BILAG and SLEDAI indices and a physician's global assessment. It has been used in the most recent clinical trials. Damage correlates with prognosis; it is assessed by the SLICC/SDI index. This index scores damage whatever the cause, disease or treatment related, or the consequence of concomitant disease. The disease activity and damage indices do not correlate well with the patient's health related quality of life (HRQoL), the degree of disability or the impact of disease. The impact of the patients' joint disease on their HRQoL is assessed via the HAQ questionnaire and the global health status via the SF-36 index, or one of the more recently described lupus specific quality of life indices [Lupus QoL]. The global assessment instruments and the BILAG index can also be used in children and adolescents with SLE. However, a modified paediatric version of the SLICC/SDI damage index is advised. Many advances have been achieved in disease activity and damage measurement in the past 20 years but the problem of how best to capture flare accurately remains.

Purpose Suicide is a major cause of death in adolescents with first-episode schizophrenia (FES). The aim of this pilot study was to compare suicide-related traits between subjects with FES and those with other psychopathologies to evaluate risk factors for suicidal behavior. Method Twenty-five inpatient adolescents with FES and a control group of 28 psychiatric inpatients matched for sex and age were assessed for depression, anger, criminal behavior, aggression, and suicidal ideation, risk, and potential. Results The adolescents with FES had significantly lower depression ( P = .003), anger ( P = .025), and criminal behavior ( P = .022) than did the controls. However, although suicide ideation was greater in the subjects with FES ( P = .003), suicide risk was significantly lower than that in controls ( P = .004). Conclusion Decreased levels of both depression and anger as part of affective constriction in the group with schizophrenia could explain why the increased suicide ideation did not lead to a higher suicide risk in these inpatients. This study highlights the importance of distinguishing between suicidal ideation and actual suicide risk. We demonstrated that thoughts of suicide do not necessarily translate into an actual risk of suicidal behavior in adolescents with schizophrenia.

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.

Pamidronate, along with other bisphosphonates, has been used for treatment of bone pain secondary to malignant involvement or metastatic disease for years. Some data, however, have also accumulated on the utility of pamidronate in a variety of benign conditions frequently handled by rheumatologists. This study aims to review the available published data regarding the potential use of pamidronate in rheumatology practice. Methods include the review of relevant articles retrieved by a PUBMED search utilizing the index term "pamidronate". All available randomized control trials, open trials, and case series, as well as properly reported case studies evaluating usage of pamidronate in rheumatic disorders, have been included in the literature review. The efficacy of pamidronate in patients with spondyloarthropathies; synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome; hypertrophic osteoarthropathy; osteoporotic vertebral fractures; chronic back pain due to disk disease or spinal stenosis; Charcot arthropathy; transient osteoporosis; and complex regional pain syndrome-I, has been demonstrated in more than 40 reports, the majority of which, however, were not controlled studies. In some of reviewed conditions, aside from providing analgesic relief, pamidronate may also have disease-modifying properties. While used in different doses in a variety of rheumatic disorders, pamidronate was generally reported to be well tolerated with an overall good safety profile. Pamidronate may represent an effective and safe choice for a spectrum of rheumatic patients, suffering from intractable musculoskeletal pain, unresponsive to traditionally recommended therapies. Large randomized, controlled studies examining the efficacy of pamidronate in the rheumatic conditions are urgently needed.

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.

Degenerative lumbar spinal stenosis, manifesting as chronic low back pain and neurogenic claudication, is an increasing chronic problem in an aging population, with limited effective conservative treatment options. Based on previous reports on the utility of subcutaneous calcitonin and two anectodal cases, we launched an open therapeutic trial of IV monthly pamidronate infusions, over a course of 3-6 months in this condition. Of 24 patients, 75% reported pain improvement, with the mean VAS score improved by 40%; while composite functional improvement in walking time, activities of daily living, and sense of well being was reported by 66%, with a mean improvement of 50%. The results of this pilot trial suggest the usefulness of this modality and warrant examination in a controlled clinical trial.

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.

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.

To investigate the prevalence of subclinical atherosclerosis among patients with psoriatic arthritis (PsA).Forty patients with PsA were enrolled. Controls were matched by age, sex, and atherosclerotic risk factors. All patients and controls underwent duplex scan of the carotid arteries. Carotid intima-media thickness (IMT) was evaluated and the presence of atherosclerotic plaques was recorded. The plaques were graded and carotid plaque index was calculated.Patients with PsA had a higher IMT (mean +/- standard deviation, 1.04 +/- 0.35 mm vs 0.88 +/- 0.29 mm in controls; p = 0.03), and had a higher carotid plaque index than did matched controls (2.3 +/- 2.6, compared to 1.12 +/- 2.09; p = 0.03). Multivariate analysis demonstrated that PsA status as well as age and triglyceride levels were associated with the presence of carotid plaque. Other traditional risk factors were more prevalent among patients with PsA; however, they were not statistically significant.Our study demonstrates that patients with PsA may have an increased prevalence of subclinical atherosclerosis. These findings may not be solely attributable to traditional risk factors alone. Special attention and strict control of atherosclerotic risk factors in patients with PsA is warranted.

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 Arthritis is estimated to precede skin psoriasis in approximately 15% of psoriatic arthritis patients (PsA) (1). However this data is based on studies published prior to the development of the Classification for Psoriatic Arthritis (CASPAR) criteria(2). Objectives The aim of this study is to characterize clinical, laboratory and radiological features that distinguish PsA patients diagnosed based on CASPAR criteria, who present with arthritis before psoriasis from those who develop either concomitant skin or joint manifestations or arthritis following psoriasis. Methods A retrospective cohort study of patients with PsA fulfilling the CASPAR criteria and followed in two rheumatology clinics was conducted. All charts were reviewed and clinical, laboratory and radiological manifestations at the first rheumatology evaluation were analyzed. Patients were divided into 3 groups according to the relation between the onset of the cutaneous psoriasis and arthritis: Group A (skin before joints), Group B (joints before skin), and Group C (simultaneous presentation). Analysis of variance and t-test were used to compare continuous variables. A Chi square test was used for categorical variables. Results Overall 160 patients were included: 121(75.6%) in Group A, 12 (7.5%) in Group B and 27 (16.9%) in Group C. Of these, 63 (39.4%) were males. Their mean age was 55.2±14.4 years. The mean age at onset of psoriasis and PsA were 39.7±16.3 and 48.3±14.3, respectively. No statistically significant difference across the groups with respect to age, gender, ethnicity and family history of psoriasis was observed. A polyarthritis pattern was observed in 81 (68.1%), 11 (91.7%), and 22 (81.5%) patients, respectively (p=0.11); oligoarthritis in 31 (26.5%), 1 (9.1%), and 4 (16%) patients, respectively (p=0.26); spinal involvement in 22(18.3%), 4 (33.3%), and 4 (14.8%) patients, respectively (p=0.37); and distal interphalangeal joint involvement in 16 (13.3%), 3 (27.3%) and 0 (0%) patients, respectively (p=0.04). No statistically significant differences were noted in the prevalence of entheseal, nail and dactylitis involvement. Radiographic studies revealed bone erosions in 28 (28%), 4 (33.3%) and 5 (25%) patients, respectively; radiographic sacroiliitis in 20 (20%), 3 (25%) and 3 (15.8%), patients, respectively; and new bone formation in 9 (8/9%), 1(8/3%) and 1(5.6%) patients, respectively, with no statistically significant differences. No statistically significant differences were noted in c-reactive protein levels, the prevalence of rheumatic factor and antinuclear antibody positivity. Conclusions A lower prevalence of PsA (7.5%) preceding skin manifestation was observed in our study using stringent CASPAR criteria compared to previous data published. No statistically significant differences in clinical, laboratory and radiological manifestations were noted across the analyzed groups. Polyarthritis is the most common pattern of PsA presentation. References Gladman DD, Shuckett R, Russeii ML, et al: Psoriatic arthritis-an analysis of 220 patients. Q J Med1987; 62:127-141. Taylor W, Gladman D, Helliwell P, et al: Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006; 54:2665-73. Disclosure of Interest None Declared

To the Editor: Pyoderma gangrenosum (PG) is an ulcerative inflammatory noninfectious disease of the skin. Treatment is mainly empirical, consisting of a combination of local and systemic treatments, including corticosteroids and immunosuppressive drugs1. In many cases, PG is associated with an underlying disease, most commonly inflammatory bowel disease, occasionally in the stromal area. PG occurs in several hematological and malignant diseases. PG has also been described in several rheumatic diseases: rheumatoid arthritis, spondyloarthropathies, systemic lupus erythematosus, Behcet’s disease, and sarcoidosis2. Hod, et al 3 reported a huge PG-like lesion as a presenting sign of antiphospholipid antibody syndrome (APS). In the literature we are aware of … Address correspondence to Dr. J. Feld, Bnai Zion Medical Center – Rheumatology, 47 Golomb Street, Haifa 31048, Israel. E-mail: joyfeld{at}gmail.com