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

Objective.: Children with clinically diagnosed juvenile psoriatic arthritis (JPsA) who were enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry (CARRA-JPsA) were classified according to pediatric International League of Associations for Rheumatology (ILAR) and adult criteria [Classification criteria for Psoriatic Arthritis (CASPAR)]. Data on demographic and clinical features at baseline and 1-year followup were analyzed and compared.Methods.: Cross-sectional analysis was performed of CARRA-JPsA patients enrolled between May 2010 and December 2013 and stratified according to age at disease onset (≤ or > 4 yrs). Features of patients fulfilling ILAR and CASPAR criteria were compared at baseline and followup using chi square, Fisher’s exact, Mann-Whitney-McNemar, Wilcoxon signed rank, and t tests, as appropriate.Results.: Among 361 children enrolled as CARRA-JPsA, 72.02% had symptom onset at > 4 years of age, with a male predominance and high prevalence of enthesitis. At followup, statistically significant improvements were reported in arthritis, dactylitis, enthesitis, psoriasis, sacroiliitis, and nail pitting, but not in health questionnaire (HQ) scores. Of the patients, 80.5% fulfilled ILAR criteria for JPsA. Fifty-two patients, whose disease fulfilled CASPAR criteria but had not been included in the JPsA cohort, manifested more enthesitis, sacroiliitis, inflammatory bowel disease and uveitis and less psoriasis.Conclusion.: The data support division of patients with JPsA into 2 clinical subgroups, according to age at disease onset. Improvement in objective findings did not correlate with changes in HQ scores. Pediatric rheumatologists currently do not diagnose JPsA in all children whose disease manifestations meet CASPAR criteria. Unification of adult and pediatric PsA classification criteria warrants consideration.

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.

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. 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. 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. 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.

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.

The aim was to assess the influence of long-term treatment with tumor necrosis factor alpha (TNF-α) inhibitors on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and atherogenic index (AI) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) patients. A retrospective cohort study was conducted on RA, PsA, and AS patients treated with TNF-α inhibitors for at least 270 days between 2001 and 2011. Levels of TC, TG, LDL, and HDL and the AI were compared with baseline values at 0–6, 6–12, 12–18, and 18–24 months. Patients were further subdivided into three groups according to their HMG CoA reductase inhibitor (statin) treatment status in order to assess their effect on the results. The records of 311 patients (152 RA, 90 PsA, and 69 AS) were reviewed. TC and TG increased following treatment with TNF-α inhibitors, from 180.85 ± 2.12 mg/dl and 116.00 ± 3.55 mg/dl at baseline to 188.12 ± 2.35 mg/dl (p = 0.02) and 132.02 ± 4.63 mg/dl at 0–6 months (p < 0.01), respectively, and to 184.88 ± 2.09 mg/dl (p = 0.02) and 129.36 ± 4.32 mg/dl at 18–24 months (p < 0.01), respectively. AI increased following treatment with TNF-α inhibitors, from –0.032 ± 0.017 at baseline to 0.004 ± 0.019 at 18–24 months (p < 0.01). LDL decreased significantly in patients who were treated with statins before and during the entire study period, from 119.97 ± 2.86 mg/dl at baseline to 104.02 ± 3.57 mg/dl at 18–24 months (p < 0.01), in contrast to an increase in LDL values in patients who did not receive statins during the study. TNF-α inhibitor treatment was associated with a significant increase in TC and TG levels and the AI. Adding statins to the treatment was associated with a significant decrease in LDL levels.