Faculty Bibliography

INTRODUCTION/BACKGROUND:Neurologic symptoms are an extremely rare presentation of Kikuchi-Fujimoto disease. We report a case of a young female patient diagnosed with Kikuchi-Fujimoto disease, presenting with neurologic symptoms compatible with aseptic meningitis, along with radiographic findings which improved with steroidal treatment. Despite the rarity of these findings, they were reported as part of the disease manifestation, however, since Kikuchi-Fujimoto disease is associated with other diseases, such as systemic lupus erythematosus (SLE), other diagnoses cannot be ruled out.

Background and Aims/UNASSIGNED:Plasma levels of soluble triggering receptor expressed on myeloid cells (sTREM-1) reflect innate immune cell activation. We sought to evaluate sTREM-1 levels in patients with acute coronary syndrome (ACS) and their predictive value for disease severity and outcome. Methods/UNASSIGNED:Plasma sTREM-1 levels were prospectively measured by ELISA in 121 consecutive patients with new-onset (≤24 h) chest pain at arrival to the emergency department (ED) and 73 healthy controls. Secondary endpoints were the association of plasma levels of sTREM-1 with day 30 and month 6 major adverse cardiovascular events (MACE) defined as death, ACS, stroke, and need for coronary revascularization, as well as with CAD severity. The primary endpoint of the study was the association of plasma sTREM-1 level at the time of admission to the ED with a diagnosis of ACS at day 30. Results/UNASSIGNED:= 0.02) at 6 months. Conclusions/UNASSIGNED:Plasma sTREM-1 levels are significantly elevated in patients with ACS and might serve as a biomarker differentiating ACS from NSCP in the ED as well as an inflammatory biomarker for coronary artery disease severity and outcome.

BACKGROUND:Rheumatic diseases have many hematological manifestations. Blood dyscrasias and other hematological abnormalities are sometimes the first sign of rheumatic disease. In addition, novel antirheumatic biological agents may cause cytopenias. SUMMARY/CONCLUSIONS:The aim of this review was to discuss cytopenias caused by systemic lupus erythematosus and antirheumatic drugs, Felty's syndrome in rheumatoid arthritis, and autoimmune hemolytic anemia, thrombosis, and thrombotic microangiopathies related to rheumatological conditions such as catastrophic antiphospholipid syndrome and scleroderma renal crisis. Key Message: The differential diagnosis of various hematological disorders should include rheumatic autoimmune diseases among other causes of blood cell and hemostasis abnormalities. It is crucial that hematologists be aware of these presentations so that they are diagnosed and treated in a timely manner.

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

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

INTRODUCTION/BACKGROUND:Mood disorders, such as anxiety and depression are extremely prevalent among patients with rheumatoid arthritis (RA). In this study we assessed the impact of treatment with tocilizumab (TCZ), an IL-6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients. METHODS:Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4 weeks and study completion. RESULTS:Ultimately, 91 patients were included in the study. The mean age was 54 years and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters respectively; HAQ-DI (r=0.4, 0.42), DAS28 (r=0.29, 0.32) and CDAI (0.28 and 0.33), all of them were statistically significant (p<0.01). CONCLUSIONS:This study has demonstrated a favorable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA.

OBJECTIVE:To amass all available evidence from randomized controlled trials regarding the safety of pulse corticosteroids therapy, in order to establish its safety. PATIENTS AND METHODS/METHODS:All electronic databases from 1/1966 up to 02/2019 were reviewed to find all randomized controlled trials comparing pulse corticosteroids to oral corticosteroids or to placebo/no treatment. Two reviewers independently extracted and recorded data regarding type of corticosteroid treatment, dosages, length of treatment and follow-up. Risk ratios (RR) with 95% (CI) for differences between pulse corticosteroids and comparator were pooled using a fixed effect meta-analysis. The primary outcome was occurrence of severe adverse events (SAEs). Secondary outcomes included any adverse events (AEs), AEs requiring discontinuation, AEs per system involved and all-cause mortality. RESULTS:A total of 64 trials were included: 18 trials which compared pulse corticosteroids to oral corticosteroids and 46 trials which compared pulse corticosteroids to placebo/no intervention. Pulse corticosteroids was not associated with increased risk for SAEs for both comparators: RR 0.77 (95% CI 0.52-1.14), and RR 0.99 (95% CI 0.93-1.06), respectively. Sensitivity analysis based on adequate allocation concealment and use of a valid AE grading did not alter the results. Subgroup analysis revealed no increased risk of specific SAEs or AEs with pulse corticosteroids compared to oral corticosteroids. CONCLUSION/CONCLUSIONS:Pulse corticosteroids was not associated with an increase risk of SAEs and should be regarded as safe.

BACKGROUND:Guidelines recommend initiation of parenteral biologic or oral target-specific disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) in rheumatoid arthritis (RA) patients who do not adequately respond to conventional DMARDs. OBJECTIVES/OBJECTIVE:To compare the preferred route of administration of bDMARDs or tsDMARDs in RA patients who were previously treated with at least one type. METHODS:A cross-sectional survey was conducted of consecutive RA patients previously prescribed bDMARDs or tsDMARDs. We analyzed the factors associated with patients' preferred route of administration. RESULTS:The cohort included 95 patients, mostly female (72.6%), seropositive (81.05%), mean age 63.4 ± 11.9 years. The oral route was preferred by 39 patients (41%) and 56 (59%) preferred the parenteral route. Most patients (65.9%) preferred to continue with their current route (P < 0.001). Switching from a current route was less common with patients who were currently using the oral route (13.3% vs. 38.2%, P = 0.04). Many patients (53.8%) who preferred the oral route had never experienced it before, while this was rare (3.6%) regarding the parenteral route (P = 0.0001). Employment status was associated with preference of the subcutaneous route over the intravenous route of bDMARDs (P = 0.01). Of the 21 patients who had previously experienced both parenteral and oral treatment, 16 (76.2%) preferred the oral route. CONCLUSIONS:RA patients preferred to continue treatment with an administration route they have already experienced. However, when choosing an unexperienced route, significantly more patients preferred the oral route. Our results strengthen the understanding of patient preferences, which could improve drug adherence, compliance, and disease outcome.

BACKGROUND:Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is an innate-immune receptor found in blood. Its presence reflects innate immune cell activation. We sought to investigate plasma sTREM-1 levels in patients with primary antiphospholipid syndrome (PAPS). METHODS:A cross-sectional, case-control design was used. Plasma sTREM-1 levels were analyzed by enzyme-linked immunosorbent assay (ELISA) in consecutive patients diagnosed with PAPS or asymptomatic antiphospholipid antibody (APLA) carriers and controls. RESULTS:The study cohort included 33 patients with PAPS, 10 asymptomatic APLA carriers, and 73 controls. Mean plasma sTREM-1 levels were significantly higher in patients with PAPS (299.2 ± 146.7 pg/ml) and thrombotic PAPS-ever (current and past thrombotic event) (327.2 ± 151.3 pg/ml) compared with controls (230.2 ± 85.5 pg/ml; p = 0.006 and p = 0.003, respectively), patients with thrombotic PAPS compared with patients with past obstetric APS (195.12 ± 58.52 pg/ml, p = 0.01) and APLA carriers (215.8 ± 51.6 pg/ml, p = 0.02), patients with current thrombotic PAPS (429.5 ± 227.5 pg/ml) compared with patients with past thrombotic PAPS (289.5 ± 94.65 pg/ml, p = 0.01), and patients with PAPS who had ever had a stroke or venous thromboembolic event compared with patients who had not (p = 0.007 and p = 0.02, respectively). On receiver operator characteristic curve analysis, plasma sTREM-1 levels differentiated patients with current thrombotic PAPS from asymptomatic APLA carriers and controls, with an area under the curve of 0.7292 (p = 0.0014) and 0.88 (p < 0.0001), respectively. Multivariate regression analysis to identify sTREM-1 predictors (thrombotic PAPS-ever, age, and sex) yielded an independent association of sTREM-1 levels with thrombotic PAPS (p < 0.0001). CONCLUSIONS:Plasma sTREM-1 levels are significantly elevated in patients with thrombotic PAPS. Levels of sTREM-1 might serve as a biomarker for thrombosis in patients with PAPS.

Background/UNASSIGNED:Uncontrolled gout can cause significant joint and organ damage and has been associated with impairments in quality of life and high economic cost. Gout has also been associated with other comorbid diseases, such as chronic kidney disease. The current study explored if healthcare resource utilization (HRU) and survival differs between patients with incident gout in the presence or absence of chronic kidney disease (CKD). Methods/UNASSIGNED:Clalit Health Services (CHS) data were used to conduct a retrospective population-based cohort study of incident gout between 1/1/2006-31/12/2009. Incident cases of gout were identified and stratified by CKD status and by age group (< 55 and 55+ years). CKD status was defined as a pre-existing diagnosis of chronic kidney disease, chronic renal failure, kidney transplantation, or dialysis at index date. Demographic and clinical characteristics, as well as healthcare resource use, were reported. Results/UNASSIGNED: = 1.50; 95% CI 1.37-1.65). Conclusions/UNASSIGNED:The current study suggests important differences exist in patient characteristics and outcomes among patients with gout and CKD. Healthcare utilization differed between sub-populations, age and comorbidities, over the study period and the 5-year mortality risk was higher for gout patients with CKD, regardless of age. Future work should explore factors associated with these outcomes and barriers to gout control in order to enhance patient management among this high-risk subgroup.