Medicine and Health Sciences Commons^™

Acthar Gel (Repository Corticotropin Injection) For Persistently Active Sle: Study Design And Baseline Characteristics From A Multicentre, Randomised, Double-Blind, Placebo-Controlled Trial, A. D. Askanase, E. Zhao, J. Zhu, E. Connolly-Strong, R. A. Furie

Journal Articles

© 2020 Author(s). Objective SLE is a chronic inflammatory autoimmune disease characterised by the excessive production of autoantibodies, immune complexes and proinflammatory cytokines. Repository corticotropin injection (RCI) is a naturally sourced complex mixture of adrenocorticotropic hormone analogues and other pituitary peptides. RCI is approved by the US Food and Drug Administration for use during an exacerbation or as maintenance therapy in select cases of SLE. This paper discusses the design and baseline characteristics of a multicentre, double-blind, randomised, placebo-controlled, 24-week clinical trial evaluating the effect of RCI in reducing disease activity for patients with persistently active SLE despite moderate-dose corticosteroid …

Cell-Bound Complement Activation Products Associate With Lupus Severity In Sle., C. Arriens, R. V. Alexander, S. Narain, A. Saxena, C. E. Collins, D. J. Wallace, E. Massarotti, J. Conklin, R. A. Furie, T. Dervieux, +11 Additional Authors

Journal Articles

OBJECTIVES: To evaluate the association between lupus severity and cell-bound complement activation products (CB-CAPs) or low complement proteins C3 and C4.

METHODS: All subjects (n=495) fulfilled the American College of Rheumatology (ACR) classification criteria for SLE. Abnormal CB-CAPs (erythrocyte-bound C4d or B-lymphocyte-bound C4d levels >99th percentile of healthy) and complement proteins C3 and C4 were determined using flow cytometry and turbidimetry, respectively. Lupus severity was estimated using the Lupus Severity Index (LSI). Statistical analysis consisted of multivariable linear regression and groups comparisons.

RESULTS: Abnormal CB-CAPs were more prevalent than low complement values irrespective of LSI levels (62% vs 38%, respectively, …

Clinical Mortality In A Large Covid-19 Cohort: Observational Study., M. Jarrett, S. Schultz, J. Lyall, J. Wang, L. Stier, M. De Geronimo, K. Nelson

Journal Articles

BACKGROUND: Northwell Health, an integrated health system in New York, has treated more than 15,000 inpatients with COVID-19 at the US epicenter of the SARS-CoV-2 pandemic.

OBJECTIVE: We describe the demographic characteristics of patients who died of COVID-19, observation of frequent rapid response team/cardiac arrest (RRT/CA) calls for non-intensive care unit (ICU) patients, and factors that contributed to RRT/CA calls.

METHODS: A team of registered nurses reviewed the medical records of inpatients who tested positive for SARS-CoV-2 via polymerase chain reaction before or on admission and who died between March 13 (first Northwell Health inpatient expiration) and April 30, 2020, …

Comparative Survival Analysis Of Immunomodulatory Therapy For Coronavirus Disease 2019 Cytokine Storm., S. Narain, D. G. Stefanov, A. S. Chau, A. G. Weber, G. Marder, B. Kaplan, P. Malhotra, O. Bloom, A. Liu, M. M. Lesser, N. Hajizadeh, Northwell Covid-19 Research Consortium

Journal Articles

BACKGROUND:Cytokine storm is a marker of coronavirus disease 2019 (COVID-19) illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes. RESEARCH QUESTION:Do immunomodulatory therapies improve survival in patients with COVID-19 cytokine storm (CCS)? STUDY DESIGN AND METHODS:We conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 patients hospitalized between March 1, 2020, and April 24, 2020, were included. CCS was defined by inflammatory markers: ferritin, > 700 ng/mL; C-reactive protein (CRP), > 30 mg/dL; or lactate dehydrogenase (LDH), > 300 U/L. Patients were subdivided into six groups: no immunomodulatory treatment (standard of care) and …

An Interim Report Of The Scleroderma Clinical Trials Consortium Working Groups, M. Baron, B. Kahaleh, E. J. Bernstein, L. Chung, P. J. Clements, C. Denton, R. T. Domsic, N. Ferdowsi, S. Narain, A. Vacca, +12 Additional Authors

Journal Articles

© The Author(s) 2018. The Scleroderma Clinical Trials Consortium represents many of the clinical researchers in the world who are interested in improving the efficiency of clinical trials in systemic sclerosis. The Scleroderma Clinical Trials Consortium has established 11 working groups to develop and validate better ways of measuring and recording multiple aspects of this heterogeneous disease. These include groups working on arthritis, disease damage, disease activity, cardiac disease, juvenile systemic sclerosis, the gastrointestinal tract, vascular component, calcinosis, scleroderma renal crisis, interstitial lung disease, and skin measurement. Members of the Scleroderma Clinical Trials Consortium may join any one or more …

Phase Iii, Multicentre, Randomised, Double-Blind, Placebo-Controlled, 104-Week Study Of Subcutaneous Belimumab Administered In Combination With Rituximab In Adults With Systemic Lupus Erythematosus (Sle): Bliss-Believe Study Protocol, Y. K. Onno Teng, I. N. Bruce, B. Diamond, R. A. Furie, R. F. Van Vollenhoven, D. Gordon, J. Groark, R. B. Henderson, M. Oldham, P. P. Tak

Journal Articles

© 2019 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Introduction Belimumab, an anti-B-lymphocyte-stimulator antibody, is approved for the treatment of active, autoantibody-positive systemic lupus erythematosus (SLE). Rituximab, a B cell-depleting anti-CD20 antibody, remains in the SLE treatment armamentarium despite failed trials in lupus nephritis and extrarenal lupus. These biologics, which operate through complementary mechanisms, might result in an enhanced depletion of circulating and tissue-resident autoreactive B lymphocytes when administered together. Thus, belimumab and rituximab combination may be a highly effective treatment of SLE. This study aims to evaluate …

Delivering Challenging News: An Illness-Trajectory Communication Curriculum For Multispecialty Oncology Residents And Fellows, D. Cannone, M. Atlas, A. Fornari, M. L. Barilla-Labarca, M. Hoffman

Journal Articles

Introduction: Published curricula to teach communication skills for postgraduate fellows in oncology are few in number despite the fact that oncologists conduct many difficult discussions with their patients and their families. Such discussions may include disclosing initial diagnosis or relapse of a patient's cancer or relaying a poor prognosis or change to palliative care. Methods: An eight-module course on communication in oncology practice was delivered over 2 months for palliative and oncology fellows and radiation oncology residents. Learners were given a precourse survey in which they were asked to rate their proficiency in various communication tasks. Each learner then participated …

Safety And Efficacy Of Belimumab Plus Standard Therapy For Up To Thirteen Years In Patients With Systemic Lupus Erythematosus, D. J. Wallace, E. M. Ginzler, J. T. Merrill, R. A. Furie, W. Stohl, W. W. Chatham, A. Weinstein, J. D. Mckay, W. J. Mccune, A. Heath, +4 Additional Authors

Journal Articles

© 2019 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology. Objective: To investigate the long-term safety and efficacy of intravenous (IV) belimumab plus standard of care (SOC) therapy for systemic lupus erythematosus (SLE) in patients with active, autoantibody-positive SLE. Methods: The study was designed as a multicenter, open-label, continuation study of IV belimumab given every 4 weeks in conjunction with SOC therapy in patients with SLE who completed a phase II, double-blind study. Adverse events (AEs) and laboratory data were monitored from the first belimumab dose (in either study) until 24 …

Monoclonal Antibody Targeting Bdca2 Ameliorates Skin Lesions In Systemic Lupus Erythematosus, R. Furie, V. P. Werth, J. F. Merola, L. Stevenson, T. L. Reynolds, H. Naik, W. Wang, R. Christmann, A. Gardet, N. Franchimont, +6 Additional Authors

Journal Articles

No abstract provided.

Randomised Prospective Trial To Assess The Clinical Utility Of Multianalyte Assay Panel With Complement Activation Products For The Diagnosis Of Sle., D. J. Wallace, R. V. Alexander, T. O'Malley, A. Khosroshahi, M. Hojjati, K. Loupasakis, J. Alper, Y. Sherrer, S. Narain, T. Dervieux, +6 Additional Authors

Journal Articles

Objective: We compared the physician-assessed diagnostic likelihood of SLE resulting from standard diagnosis laboratory testing (SDLT) to that resulting from multianalyte assay panel (MAP) with cell-bound complement activation products (MAP/CB-CAPs), which reports a two-tiered index test result having 80% sensitivity and 86% specificity for SLE.

Methods: Patients (n=145) with a history of positive antinuclear antibody status were evaluated clinically by rheumatologists and randomised to SDLT arm (tests ordered at the discretion of the rheumatologists) or to MAP/CB-CAPs testing arm. The primary endpoint was based on the change in the physician likelihood of SLE on a five-point Likert scale collected before …

Long-Term Safety And Efficacy Of Belimumab In Patients With Systemic Lupus Erythematosus A Continuation Of A Seventy-Six-Week Phase Iii Parent Study In The United States, R. A. Furie, D. J. Wallace, C. Aranow, J. Fettiplace, B. Wilson, P. Mistry, D. A. Roth, D. Gordon

Journal Articles

No abstract provided.

Development Of A Molecular Signature To Monitor Pharmacodynamic Responses Mediated By In Vivo Administration Of Glucocorticoids, Y. Hu, J. A. Carman, D. Holloway, S. Kansal, L. Fan, C. Goldstine, D. Lee, J. E. Somerville, R. Furie, S. G. Nadler, +7 Additional Authors

Journal Articles

© 2018 American College of Rheumatology. Objective: To develop an objective, readily measurable pharmacodynamic biomarker of glucocorticoid (GC) activity. Methods: Genes modulated by prednisolone were identified from in vitro studies using peripheral blood mononuclear cells from normal healthy volunteers. Using the criteria of a >2-fold change relative to vehicle controls and an adjusted P value cutoff of less than 0.05, 64 up-regulated and 18 down-regulated genes were identified. A composite score of the up-regulated genes was generated using a single-sample gene set enrichment analysis algorithm. Results: GC gene signature expression was significantly elevated in peripheral blood leukocytes from normal healthy …

Erythrocyte-Bound C4d In Combination With Complement And Autoantibody Status For The Monitoring Of Sle., J. T. Merrill, M. A. Petri, J. Buyon, R. Ramsey-Goldman, K. Kalunian, C. Putterman, J. Conklin, R. A. Furie, T. Dervieux

Journal Articles

Background: We examined the usefulness of erythrocyte-bound C4d (EC4d) to monitor disease activity in SLE.

Methods: Data and blood samples were collected from three different studies, each of which included longitudinal evaluations using the Physicians Global Assessment (PGA) of disease activity and the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI), which was assessed without anti-double-stranded DNA (dsDNA) and low complement C3/C4 (clinical SELENA-SLEDAI). EC4d levels were determined using flow cytometry; other laboratory measures included antibodies to dsDNA, C3 and C4 proteins. Relationships between clinical SELENA-SLEDAI, PGA and the laboratory measures were analysed using …

A 6-Month, Multicenter, Open-Label Study Of Fixed Dose Naproxen/Esomeprazole In Adolescent Patients With Juvenile Idiopathic Arthritis, D. J. Lovell, J. A. Dare, M. Francis-Sedlak, J. Ball, B. D. Lamoreaux, E. Von Scheven, A. Reinhardt, R. Jerath, B. Gottlieb, R. J. Holt, +6 Additional Authors

Journal Articles

© 2018 The Author(s). Background: Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age. JIA is the most common chronic rheumatic disease in children. NSAIDs have been the mainstay of initial management with naproxen (NAP) being commonly used, but they may cause serious side effects such as gastric ulcers which can be reduced by concomitant administration of proton pump inhibitors, such as esomeprazole (ESO). Methods: Primary objective was to evaluate the safety and tolerability of 3 fixed doses of NAP/ESO in JIA patients aged …

Idiopathic Pancreatitis As A Rare Gastrointestinal Manifestation Of Myotonic Muscular Dystrophy., N. Kello

Journal Articles

Myotonic muscular dystrophy (DM) is a multi-system disorder affecting skeletal muscles as well as smooth and cardiac muscles. Patients with DM experience disturbances in gastrointestinal motility; however, pancreatobiliary manifestations have rarely been described. We report the case of a 58-year-old male with MD who presented with a sudden onset of vomiting and abdominal pain. Laboratory and radiological findings were consistent with acute pancreatitis. No identifiable cause of pancreatitis could be identified despite an extensive workup. Sphincter of Oddi dysfunction (SOD) was felt to be the most likely cause of our patient's acute pancreatitis. SOD leading to acute pancreatitis results from …

Lessons Learned From Bone Marrow Failure In Systemic Lupus Erythematosus: Case Reports And Review Of The Literature, E. Anderson, B. Shah, A. Davidson, R. Furie

Journal Articles

© 2017 Elsevier Inc. Objective: In the present review, four new cases of bone marrow failure are presented and the potential contribution of systemic lupus erythematosus (SLE) is discussed. Furthermore, a comprehensive literature review of cases of autoimmune myelofibrosis (AIMF), aplastic anemia (AA), and paroxysmal nocturnal hemoglobinuria (PNH) with concurrent SLE aims to allow their direct comparison. Based on a clearer characterization of reported cases and our own experience, diagnostic and therapeutic strategies of these disorders in SLE are proposed based on lessons learned from the present and previous cases. Methods: A literature search was done in PubMed, accessed via …

Development Of A Novel Renal Activity Index Of Lupus Nephritis In Children & Young Adults, H. I. Brunner, M. Bennett, K. Abulaban, M. Klein-Gitelman, K. O'Neil, L. Tucker, S. Ardoin, K. Rouster-Stevens, B. A. Eberhard, P. Devarajan, +8 Additional Authors

Journal Articles

BACKGROUND: Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histological LN activity. METHODS: We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n=47) at the time of kidney biopsy. Histological LN activity was measured by the NIH Activity Index (NIH-AI) and the Tubulointerstitial Activity Index (TIAI). High LN-activity status (vs. moderate/low) was defined as NIH-AI scores > 10 (vs.5 (vs.92% accuracy and LN-activityTIAI status with …

Validation Of The Lupus Nephritis Clinical Indices In Childhood-Onset Systemic Lupus Erythematosus, R. Mina, K. Abulaban, M. Klein-Gitelman, A. Eberhard, S. Ardoin, N. Singer, K. Onel, L. Tucker, K. O'Neil, H. I. Brunner, +8 Additional Authors

Journal Articles

OBJECTIVE: To validate clinical indices of lupus nephritis (LN) activity and damage when used in children against the criterion standard of kidney biopsy findings. METHODS: In 83 children requiring kidney biopsy the SLE Disease Activity Index Renal Domain (SLEDAI-R); British Isles Lupus Assessment Group index Renal Domain (BILAG-R), Systemic Lupus International Collaborating Clinics Renal Activity (SLICC-RAS) and Damage Index Renal Domain (SDI-R) were measured. Fixed effect and logistic models were done to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low/moderate vs. high LN-activity [NIH Activity Index (NIH-AI) score:10; Tubulointerstitial Activity Index (TIAI) score:5) or the absence vs. presence …

Effects Of Obesity On Health-Related Quality Of Life In Juvenile-Onset Systemic Lupus Erythematosus, R. Mina, M. S. Klein-Gitelman, S. Nelson, B. A. Eberhard, G. Higgins, N. G. Singer, K. Onel, L. Tucker, K. M. O'Neil, H. I. Brunner, +4 Additional Authors

Journal Articles

OBJECTIVE: This study evaluated the effects of obesity on health-related quality of life (HRQOL) measures in juvenile-onset systemic lupus erythematosus (jSLE). METHODS: Obesity was defined as a body mass index (BMI) >/=95th percentile according to the Sex-specific Center for Disease Control BMI-For-Age Charts and determined in a multicenter cohort of jSLE patients. In this secondary analysis, the domain and summary scores of the Pediatric Quality of Life (PedsQL) Inventory and the Child Health Questionnaire (CHQ) of obese jSLE patients were compared to those of non-obese jSLE patients as well as historical obese and non-obese healthy controls. Mixed-effects modeling was performed …

Safety And Efficacy Of Belimumab To Treat Systemic Lupus Erythematosus In Academic Clinical Practices, J. S. Hui-Yuen, A. Reddy, J. Taylor, X. Li, A. H. Eichenfield, L. M. Bermudez, A. J. Starr, L. F. Imundo, R. A. Furie, A. Askanase, +7 Additional Authors

Journal Articles

No abstract provided.

Platelets Are Required For Enhanced Activation Of The Endothelium And Fibrinogen In A Mouse Thrombosis Model Of Aps, V. Proulle, R. A. Furie, G. Merrill-Skoloff, B. C. Furie, B. Furie

Journal Articles

Antiphospholipid syndrome (APS) is defined by thrombosis, fetal loss, and the presence of antiphospholipid antibodies, including anti-beta 2-glycoprotein-1 autoantibodies (anti-beta 2GP1) that have a direct role in the pathogenesis of thrombosis in vivo. The cellular targets of the anti-beta 2GP1autoantibody/beta 2GP1complex in vivo were studied using a laser-induced thrombosis model of APS in a live mouse and human anti-beta 2GP1 autoantibodies affinity-purified from APS patients. Cell binding of fluorescently labeled beta 2GP1 and anti-beta 2GP1 autoantibodies revealed their colocalization on the platelet thrombus but not the endothelium. Anti-beta 2GP1 autoantibodies enhanced platelet activation, monitored by calcium mobilization, and endothelial activation, …

Randomized, Double-Blind, Placebo-Controlled Trial Of The Efficacy And Safety Of Rilonacept In The Treatment Of Systemic Juvenile Idiopathic Arthritis, N. T. Ilowite, K. Prather, Y. Lokhnygina, L. E. Schanberg, M. Elder, D. Milojevic, J. W. Verbsky, S. J. Spalding, B. S. Gottlieb, C. I. Sandborg, +12 Additional Authors

Journal Articles

OBJECTIVE: To assess the efficacy and safety of rilonacept, an interleukin-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. METHODS: An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multicenter design, followed by an open-label phase. Seventy-one children who had active arthritis in >/=2 joints were randomized (1:1) to the 2 arms of the study. Patients in the rilonacept arm received rilonacept (loading dose 4.4 mg/kg followed by 2.2 mg/kg weekly, subcutaneously) beginning on day 0. Patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by …

Safety Of Celecoxib And Nonselective Nonsteroidal Anti-Inflammatory Drugs In Juvenile Idiopathic Arthritis: Results Of The Phase 4 Registry, R. E. Sobel, D. J. Lovell, H. I. Brunner, J. E. Weiss, P. W. Morris, B. S. Gottlieb, E. C. Chalom, L. K. Jung, K. B. Onel, E. H. Giannini, +6 Additional Authors

Journal Articles

BACKGROUND: This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs). METHODS: Children aged >/=2 to-negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (

Cell-Bound Complement Activation Products In Systemic Lupus Erythematosus: Comparison With Anti-Double-Stranded Dna And Standard Complement Measurements, C. Putterman, R. Furie, R. Ramsey-Goldman, A. Askanase, J. Buyon, K. Kalunian, W. W. Chatham, E. Massarotti, K. Kirou, T. Dervieux, +10 Additional Authors

Journal Articles

OBJECTIVE: To compare the performance characteristics of cell-bound complement (C4d) activation products (CBCAPS) on erythrocyte (EC4d) and B cells (BC4d) with antibodies to double-stranded DNA (anti-dsDNA) and complement C3 and C4 in systemic lupus erythematosus (SLE). METHODS: The study enrolled 794 subjects consisting of 304 SLE and a control group consisting of 285 patients with other rheumatic diseases and 205 normal individuals. Anti-dsDNA and other autoantibodies were measured using solid-phase immunoassays while EC4d and BC4d were determined using flow cytometry. Complement proteins were determined using immunoturbidimetry. Disease activity in SLE was determined using a non-serological Systemic Lupus Erythematosus Disease Activity …

A Comparison Of The Malignancy Incidence Among Patients With Psoriatic Arthritis And Patients With Rheumatoid Arthritis In A Large Us Cohort, R. L. Gross, J. S. Schwartzman-Morris, M. Krathen, G. Reed, H. Chang, K. C. Saunders, M. C. Fisher, J. D. Greenberg, C. Putterman, A. Broder, +3 Additional Authors

Journal Articles

OBJECTIVE: To compare the incidence rates of malignancy among patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) in the Consortium of Rheumatology Researchers of North America (CORRONA) registry. METHODS: We analyzed 2,970 patients with PsA (7,133 patient-years of followup) and 19,260 patients with RA (53,864 patient-years of followup). Using a standardized adjudication process, we identified 40 confirmed malignancies in the patients with PsA and 307 confirmed malignancies in those with RA. Incidence rates were calculated per 100 patient-years. Incidence rate ratios were estimated, with adjustment for age, sex, disease duration, body mass index, disease activity, year of …

Dose-Escalation Of Human Anti-Interferon-Alpha Receptor Monoclonal Antibody Medi-546 In Subjects With Systemic Sclerosis: A Phase 1, Multicenter, Open Label Study, A. Goldberg, T. Geppert, E. Schiopu, T. Frech, V. Hsu, R. W. Simms, S. L. Peng, Y. H. Yao, N. Elgeioushi, S. Yoo, +2 Additional Authors

Journal Articles

Introduction: Type I interferons (IFNs) are implicated in the pathogenesis of systemic sclerosis (SSc). MEDI-546 is an investigational human monoclonal antibody directed against the type I IFN receptor. This Phase 1 study evaluated the safety/tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of single and multiple intravenous doses of MEDI-546 in adults with SSc. Methods: Subjects (>= 18 years) with SSc were enrolled in an open-label, dose-escalation study to receive single (0.1, 0.3, 1.0, 3.0, 10.0, or 20.0 mg/kg), or 4 weekly intravenous doses (0.3, 1.0, or 5.0 mg/kg/week) of MEDI-546. Subjects were followed for 12 weeks. Safety assessments included …

Efficacy And Safety Of Abatacept In Lupus Nephritis A Twelve-Month, Randomized, Double-Blind Study, R. Furie, K. Nicholls, T. T. Cheng, F. Houssiau, R. Burgos-Vargas, S. L. Chen, J. L. Hillson, S. Meadows-Shropshire, M. Kinaszczuk, J. T. Merrill

Journal Articles

Objective. To compare the efficacy and safety of intravenous (IV) abatacept, a selective T cell costimulation modulator, versus placebo for the treatment of active class III or IV lupus nephritis, when used on a background of mycophenolate mofetil and glucocorticoids. Methods. This was a 12-month, randomized, phase II/III, multicenter, international, double-blind study. A total of 298 patients were treated in 1 of 3 IV treatment arms: placebo, abatacept at the standard weight-tiered dose (approximating 10 mg/kg), or abatacept at 30 mg/kg for 3 months, followed by the standard weight-tiered dose (abatacept 30/10). The primary end point, time to confirmed complete …