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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.

ObjectiveWe aimed to characterize the course of COVID-19 in autoimmune inflammatory rheumatic disease (AIIRD) patients in Israel, taking into consideration several remarkable aspects, including the outcomes of the different outbreaks, the effect of vaccination campaigns, and AIIRD activity post-recovery.MethodsWe established a national registry of AIIRD patients diagnosed with COVID-19, including demographic data, AIIRD diagnosis, duration and systemic involvement, comorbidities, date of COVID-19 diagnosis, clinical course, and dates of vaccinations. COVID-19 was diagnosed by a positive SARS-CoV-2 polymerase chain reaction.ResultsIsrael experienced 4 outbreaks of COVID-19 until 30.11.2021. The first three outbreaks (1.3.2020 – 30.4.2021) comprised 298 AIIRD patients. 64.9% had a mild disease and 24.2% had a severe course; 161 (53.3%) patients were hospitalized, 27 (8.9%) died. The 4th outbreak (delta variant), starting 6 months after the beginning of the vaccination campaign comprised 110 patients. Despite similar demographic and clinical characteristics, a smaller proportion of AIIRD patients had negative outcomes as compared to the first 3 outbreaks, with regards to severity (16 patients,14.5%), hospitalization (29 patients, 26.4%) and death (7 patients, 6.4%). COVID-19 did not seem to influence the AIIRD activity 1-3 months post-recovery.ConclusionsCOVID-19 is more severe and has an increased mortality in active AIIRD patients with systemic involvement, older age and comorbidities. Vaccination with 3 doses of the mRNA vaccine against SARS-CoV-2 protected from severe COVID-19, hospitalization and death during the 4th outbreak. The pattern of spread of COVID-19 in AIIRD patients was similar to the general population.

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.

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.

Development of autoantibodies following BNT162b2 mRNA COVID-19 vaccination and their association with disease flares in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and the general population: results of 1-year prospective follow-up study. We conducted a prospective study aimed at investigating the incidence of appearance of autoantibodies (antinuclear, antiphospholipid, and rheumatoid factor) in the sera of 463 adult patients with AIIRD compared to 55 controls from the general population prior to, and following the second and third vaccine doses, and at 1-year of follow-up. Pre- and post-vaccination disease activity indices and the association of autoantibodies with rheumatic disease flares and new onset AIIRD were examined. Autoantibody development of any type in AIIRD patients vs. the controls was 4.0% (vs. 6.7%, p = 0.423) following two vaccine doses and 7.6% (vs. 0%, p = 0.152) after three doses. There was no significant difference in sex, age, or disease-type among individuals with and without autoantibody development, regardless of the immunosuppressant use. More patients developed autoantibodies following the third than the second vaccine dose (p = 0.004). Disease flares occurred in 5.8% and 7.2% of AIIRD patients following second and third vaccine doses, respectively, with autoantibody production increasing the risk of flares following the second (p = 0.002) and third (p = 0.004) vaccine doses. BNT162b2 vaccination resulted in the development of autoantibodies in a minority of AIIRD patients and controls. Autoantibody development was associated with disease flares in patients, but no new-onset autoimmunity was observed.

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.

ObjectiveThe 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations provide an evidence-based guide for selecting therapy based on the individual's disease features. Beyond the disease features and associated conditions (eg, uveitis and inflammatory bowel disease), comorbidities play an important role in selecting therapy for an individual patient.MethodsWe performed a systematic literature review. We examined the available evidence to inform treatment selection based on the presence or absence of comorbidities in psoriatic arthritis (PsA).ResultsCommon comorbidities in PsA that may affect treatment selection include presence of baseline cardiovascular disease (CVD) or high risk for CVD, obesity and metabolic syndrome, liver disease, mood disorders, including depression in particular, chronic infections, malignancies, osteoporosis, and fibromyalgia and/or central sensitization.ConclusionComorbidities may influence both the effectiveness of a given therapy but also the potential for adverse events. It is important to assess for the presence of comorbidities prior to therapy selection.

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

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

Treatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX). We analyzed 108 AIIRD-RTX patients and 122 immunocompetent controls vaccinated with BNT162b2 mRNA participating in a multicenter vaccination study. Immunogenicity was defined by positive anti-SARS-CoV-2 S1/S2 IgG. We used a stepwise backward multiple logistic regression to identify predicting factors for a positive immunogenic response to vaccination and develop a predicting calculator, further validated in an independent cohort of AIIRD-RTX BNT162b2 mRNA vaccinated patients (n = 48). AIIRD-RTX patients who mounted a seropositive immunogenic response significantly differed from patients who did not by a lower number of RTX courses (median (range) 3 (1–10) vs. 5 (1–15), p = 0.007; lower cumulative RTX dose (mean ± SD) 6943.11 ± 5975.74 vs. 9780.95 ± 7240.12 mg, p = 0.033; higher IgG level prior to last RTX course (mean ± SD), 1189.78 ± 576.28 vs. 884.33 ± 302.31 mg/dL, p = 0.002), and extended interval between RTX treatment and vaccination, 469.82 ± 570.39 vs. 162.08 ± 160.12 days, p = 0.0009, respectively. Patients with ANCA-associated vasculitis and inflammatory myositis had a low likelihood of a seropositive immunogenic response compared to patients with rheumatoid arthritis, odds ratio (OR) 0.209, 95% confidence interval (CI) 0.046–0.96, p = 0.044 and OR 0.189, 95% CI 0.036–0.987, p = 0.048, respectively. Based on these findings, we constructed a calculator predicting the probability of a seropositive immunogenic response following BNT162b2 mRNA vaccination which performed with 90.5% sensitivity, 59.3% specificity, and 63.3% positive and 88.9% negative predictive values. In summary, the predicting calculator could guide clinicians for optimal timing of BNT162b2 mRNA vaccination in AIIRD-RTX patients.

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.

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.

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

Objective.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.

Background: Emerging Psoriatic arthritis (PsA) treatments have had a great impact on treatment strategies and healthcare costs in PsA disease management. Therefore, investigating changes in therapy is important to patients, healthcare providers, and healthcare payers alike. Objectives: To describe changes in treatment strategies and management of PsA patients in a real-world setting over the years 2000-2017 since the introduction of diverse novel biologic disease modifying anti-rheumatic drugs (bDMARDS). Methods: A retrospective study was performed using the previously-tested and validated database of Clalit Health Services, the database of the largest healthcare provider in Israel. The database includes continuous real-time input from pharmaceutical and medical digital systems regarding prescribed and dispensed medications. In this study, data on all conventional DMARDs (cDMARDs) and bDMARDs dispensed to the PsA patient cohort from 2000-2017 was retrieved. In Israel, all patients are eligible for bDMARDS following treatment failure of at least 2 cDMARDS with bDMARDs used in different sequences and/or combinations based on patient and physician preference. Of note, Etanercept and infliximab are available on the Israeli market since 2000, adalimumab since 2002, Golimumab since 2006 and Ustekinumab since 2014. Descriptive statistics, including means (standard deviations) for continuous variables and frequencies (%) for categorical variables, were used. Results: The study included 5062 PsA patients. Data showed an increase in use of bDMARDs in recent years (Fig 1). The trend in increasing use of bDMARDS was not affected by age, sex, and ethnicity. Etanercept was the most commonly used bDMARD (10.1%) over time, whereas, methotrexate was the most commonly used cDMARD (25.9%). A decrease in use of infliximab was noted along with the introduction of adimumab, golimumab and ustekinumab. Notably, a decrease in the utilization of cDMARDs, but not corticosteroid use, was seen with the advent of bDMARDs (Fig 2). However, this decrease in cDMARD use was not observed in patients treated with infliximab [Correlation Coefficient 2.69% (-47.5%, 51.6%), P=0.921]. Conclusion: More PsA patients are using bDMARDs in recent years in lieu of cDMRADS. This change in PsA management highlights a need for further research on the relative safety efficacy and cost of biologic agents to better guide evidence-based treatment decisions. Disclosure of interests: amir Haddad: None declared, Faten Tatour: None declared, Tal Gazitt: None declared, Ilan Feldhamer: None declared, Irina Bergman: None declared, arnon Cohen Grant/research support from: Prof. Arnon Cohen received research grants from Janssen, Novartis and abbVie and Sanofi, Consultant for: Prof. Arnon Cohen served as a consultant, advisor for abbVie; amgen; Boehringer ingelheim; Dexcel pharma; Janssen, Lilly; Neopharm; Novartis, Perrigo; Pfizer; Rafa; Sanofi, Speakers bureau: Prof. Arnon Cohen served as speaker for abbVie; amgen; Boehringer ingelheim; Dexcel pharma; Janssen, Lilly; Neopharm; Novartis, Perrigo; Pfizer; Rafa; Sanofi, Devy Zisman Grant/research support from: Dr D Zisman received research grants from Pfizer, Janssen, Consultant for: Dr D Zisman served as a consultant, for Pfizer, abbvie, Novartis, Ellie-Lilly, Sanofi, Speakers bureau: Dr D Zisman served as a speaker for abbVie, Janssen, Lilly, Novartis, Pfizer, Sanofi

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

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

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

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

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

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

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

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.

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

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

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.

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

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.