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https://www.readbyqxmd.com/read/27367267/canakinumab-for-the-treatment-of-active-systemic-juvenile-idiopathic-arthritis
#1
Janet E Orrock, Norman T Ilowite
INTRODUCTION: Canakinumab, a fully human monoclonal antibody against interleukin-1β, is a relatively new medication approved for treatment of systemic juvenile idiopathic arthritis (SJIA). Here, we review data supporting use of canakinumab for patients with active SJIA, as compared to other available biologic medications. AREAS COVERED: This article provides an overview of chemistry of canakinumab as well as the phase II and phase III trials that led to approval for treatment of active SJIA...
August 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27306623/biologics-in-pediatric-rheumatology-quo-vadis
#2
REVIEW
Yonit Sterba, Norman Ilowite
The past two decades have brought immense satisfaction to pediatric rheumatologists and families of children with rheumatologic diseases. We have been able to better classify, recognize, and diagnose rheumatologic diseases, but most importantly, the discovery of biologic therapies and their efficacy and relative safety in treating multiple rheumatologic conditions, improving quality of life for the patients we care for. We will review the advances of the past two decades and discuss potential areas for new discoveries...
July 2016: Current Rheumatology Reports
https://www.readbyqxmd.com/read/26973882/autoimmune-response-to-transthyretin-in-juvenile-idiopathic-arthritis
#3
Cristina C Clement, Halima Moncriefe, Aditi Lele, Ginger Janow, Aniuska Becerra, Francesco Bauli, Fawzy A Saad, Giorgio Perino, Cristina Montagna, Neil Cobelli, John Hardin, Lawrence J Stern, Norman Ilowite, Steven A Porcelli, Laura Santambrogio
Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatological condition. Although it has been proposed that JIA has an autoimmune component, the autoantigens are still unknown. Using biochemical and proteomic approaches, we identified the molecular chaperone transthyretin (TTR) as an antigenic target for B and T cell immune responses. TTR was eluted from IgG complexes and affinity purified from 3 JIA patients, and a statistically significant increase in TTR autoantibodies was observed in a group of 43 JIA patients...
February 2016: JCI Insight
https://www.readbyqxmd.com/read/26865703/2016-classification-criteria-for-macrophage-activation-syndrome-complicating-systemic-juvenile-idiopathic-arthritis-a-european-league-against-rheumatism-american-college-of-rheumatology-paediatric-rheumatology-international-trials-organisation-collaborative
#4
Angelo Ravelli, Francesca Minoia, Sergio Davì, AnnaCarin Horne, Francesca Bovis, Angela Pistorio, Maurizio Aricò, Tadej Avcin, Edward M Behrens, Fabrizio De Benedetti, Lisa Filipovic, Alexei A Grom, Jan-Inge Henter, Norman T Ilowite, Michael B Jordan, Raju Khubchandani, Toshiyuki Kitoh, Kai Lehmberg, Daniel J Lovell, Paivi Miettunen, Kim E Nichols, Seza Ozen, Jana Pachlopnik Schmid, Athimalaipet V Ramanan, Ricardo Russo, Rayfel Schneider, Gary Sterba, Yosef Uziel, Carol Wallace, Carine Wouters, Nico Wulffraat, Erkan Demirkaya, Hermine I Brunner, Alberto Martini, Nicolino Ruperto, Randy Q Cron
To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection)...
March 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/26848401/expert-consensus-on-dynamics-of-laboratory-tests-for-diagnosis-of-macrophage-activation-syndrome-complicating-systemic-juvenile-idiopathic-arthritis
#5
Angelo Ravelli, Francesca Minoia, Sergio Davì, AnnaCarin Horne, Francesca Bovis, Angela Pistorio, Maurizio Aricò, Tadej Avcin, Edward M Behrens, Fabrizio De Benedetti, Alexandra Filipovic, Alexei A Grom, Jan-Inge Henter, Norman T Ilowite, Michael B Jordan, Raju Khubchandani, Toshiyuki Kitoh, Kai Lehmberg, Daniel J Lovell, Paivi Miettunen, Kim E Nichols, Seza Ozen, Jana Pachlopnik Schmid, Athimalaipet V Ramanan, Ricardo Russo, Rayfel Schneider, Gary Sterba, Yosef Uziel, Carol Wallace, Carine Wouters, Nico Wulffraat, Erkan Demirkaya, Hermine I Brunner, Alberto Martini, Nicolino Ruperto, Randy Q Cron
OBJECTIVE: To identify which laboratory tests that change over time are most valuable for the timely diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA). METHODS: A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of experts was first asked to evaluate 115 profiles of patients with MAS, which included the values of laboratory tests at the pre-MAS visit and at MAS onset, and the change in values between the two time points...
2016: RMD Open
https://www.readbyqxmd.com/read/26747737/altered-signaling-in-systemic-juvenile-idiopathic-arthritis-monocytes
#6
Claudia Macaubas, Elizabeth Wong, Yujuan Zhang, Khoa D Nguyen, Justin Lee, Diana Milojevic, Susan Shenoi, Anne M Stevens, Norman Ilowite, Vivian Saper, Tzielan Lee, Elizabeth D Mellins
Systemic juvenile idiopathic arthritis (sJIA) is characterized by systemic inflammation and arthritis. Monocytes are implicated in sJIA pathogenesis, but their role in disease is unclear. The response of sJIA monocytes to IFN may be dysregulated. We examined intracellular signaling in response to IFN type I (IFNα) and type II (IFNγ) in monocytes during sJIA activity and quiescence, in 2 patient groups. Independent of disease activity, monocytes from Group 1 (collected between 2002 and 2009) showed defective STAT1 phosphorylation downstream of IFNs, and expressed higher transcript levels of SOCS1, an inhibitor of IFN signaling...
February 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/26598658/hla-drb1-11-and-variants-of-the-mhc-class-ii-locus-are-strong-risk-factors-for-systemic-juvenile-idiopathic-arthritis
#7
MULTICENTER STUDY
Michael J Ombrello, Elaine F Remmers, Ioanna Tachmazidou, Alexei Grom, Dirk Foell, Johannes-Peter Haas, Alberto Martini, Marco Gattorno, Seza Özen, Sampath Prahalad, Andrew S Zeft, John F Bohnsack, Elizabeth D Mellins, Norman T Ilowite, Ricardo Russo, Claudio Len, Maria Odete E Hilario, Sheila Oliveira, Rae S M Yeung, Alan Rosenberg, Lucy R Wedderburn, Jordi Anton, Tobias Schwarz, Anne Hinks, Yelda Bilginer, Jane Park, Joanna Cobb, Colleen L Satorius, Buhm Han, Elizabeth Baskin, Sara Signa, Richard H Duerr, J P Achkar, M Ilyas Kamboh, Kenneth M Kaufman, Leah C Kottyan, Dalila Pinto, Stephen W Scherer, Marta E Alarcón-Riquelme, Elisa Docampo, Xavier Estivill, Ahmet Gül, Paul I W de Bakker, Soumya Raychaudhuri, Carl D Langefeld, Susan Thompson, Eleftheria Zeggini, Wendy Thomson, Daniel L Kastner, Patricia Woo
Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata...
December 29, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26314788/2016-classification-criteria-for-macrophage-activation-syndrome-complicating-systemic-juvenile-idiopathic-arthritis-a-european-league-against-rheumatism-american-college-of-rheumatology-paediatric-rheumatology-international-trials-organisation-collaborative
#8
COMPARATIVE STUDY
Angelo Ravelli, Francesca Minoia, Sergio Davì, AnnaCarin Horne, Francesca Bovis, Angela Pistorio, Maurizio Aricò, Tadej Avcin, Edward M Behrens, Fabrizio De Benedetti, Lisa Filipovic, Alexei A Grom, Jan-Inge Henter, Norman T Ilowite, Michael B Jordan, Raju Khubchandani, Toshiyuki Kitoh, Kai Lehmberg, Daniel J Lovell, Paivi Miettunen, Kim E Nichols, Seza Ozen, Jana Pachlopnik Schmid, Athimalaipet V Ramanan, Ricardo Russo, Rayfel Schneider, Gary Sterba, Yosef Uziel, Carol Wallace, Carine Wouters, Nico Wulffraat, Erkan Demirkaya, Hermine I Brunner, Alberto Martini, Nicolino Ruperto, Randy Q Cron
OBJECTIVE: To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). METHODS: A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection)...
March 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/26314396/rate-and-clinical-presentation-of-macrophage-activation-syndrome-in-patients-with-systemic-juvenile-idiopathic-arthritis-treated-with-canakinumab
#9
Alexei A Grom, Norman T Ilowite, Virginia Pascual, Hermine I Brunner, Alberto Martini, Daniel Lovell, Nicolino Ruperto, Karolynn Leon, Karine Lheritier, Ken Abrams
OBJECTIVE: In pivotal trials, canakinumab has been shown to be effective in the treatment of systemic juvenile idiopathic arthritis (JIA), but reported adverse events have included macrophage activation syndrome (MAS). This study was undertaken to assess the impact of canakinumab on MAS incidence. METHODS: An independent MAS Adjudication Committee (MASAC), consisting of 3 of the authors, was convened, and a search of databases from clinical studies of canakinumab treatment in systemic JIA was performed using MASAC-specified adverse event terms to identify potential MAS events...
January 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/26294075/novel-treatment-options-for-juvenile-idiopathic-arthritis
#10
REVIEW
Katherine A Steigerwald, Norman T Ilowite
The purpose of this review is to summarize the newer and possible future treatments for the arthritis and systemic features in children with juvenile idiopathic arthritis (JIA), including evidence supporting their efficacy and safety.
2015: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/25511916/reply-to-pmid-24839206
#11
LETTER
Norman T Ilowite
No abstract text is available yet for this article.
March 2015: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/25331530/novel-method-to-collect-medication-adverse-events-in-juvenile-arthritis-results-from-the-childhood-arthritis-and-rheumatology-research-alliance-enhanced-drug-safety-surveillance-project
#12
MULTICENTER STUDY
Sarah Ringold, Audrey Hendrickson, Leslie Abramson, Timothy Beukelman, Peter R Blier, John Bohnsack, Elizabeth C Chalom, Harry L Gewanter, Beth Gottlieb, Roger Hollister, Joyce Hsu, Andrea Hudgins, Norman T Ilowite, Marisa Klein-Gitelman, Carol Lindsley, Jorge M Lopez Benitez, Daniel J Lovell, Tom Mason, Diana Milojevic, Lakshmi N Moorthy, Kabita Nanda, Karen Onel, Sampath Prahalad, C Egla Rabinovich, Linda Ray, Kelly Rouster-Stevens, Natasha Ruth, Michael Shishov, Steven Spalding, Reema Syed, Matthew Stoll, Richard K Vehe, Jennifer E Weiss, Andrew J White, Carol A Wallace, Rachel E Sobel
OBJECTIVE: Few data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product-based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4-year (2008-2012) EDSSP. METHODS: Participating physicians were surveyed monthly to ascertain whether their JIA patients experienced an SAE or IME...
April 2015: Arthritis Care & Research
https://www.readbyqxmd.com/read/25079592/rilonacept-pharmacokinetics-in-children-with-systemic-juvenile-idiopathic-arthritis
#13
RANDOMIZED CONTROLLED TRIAL
Julie Autmizguine, Michael Cohen-Wolkowiez, Norman Ilowite
No abstract text is available yet for this article.
January 2015: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/25044674/performance-of-current-guidelines-for-diagnosis-of-macrophage-activation-syndrome-complicating-systemic-juvenile-idiopathic-arthritis
#14
Sergio Davì, Francesca Minoia, Angela Pistorio, AnnaCarin Horne, Alessandro Consolaro, Silvia Rosina, Francesca Bovis, Rolando Cimaz, Maria Luz Gamir, Norman T Ilowite, Isabelle Kone-Paut, Sheila Knupp Feitosa de Oliveira, Deborah McCurdy, Clovis Artur Silva, Flavio Sztajnbok, Elena Tsitsami, Erbil Unsal, Jennifer E Weiss, Nico Wulffraat, Mario Abinun, Amita Aggarwal, Maria Teresa Apaz, Itziar Astigarraga, Fabrizia Corona, Ruben Cuttica, Gianfranco D'Angelo, Eli M Eisenstein, Soad Hashad, Loredana Lepore, Velma Mulaosmanovic, Susan Nielsen, Sampath Prahalad, Donato Rigante, Valda Stanevicha, Gary Sterba, Gordana Susic, Syuji Takei, Ralf Trauzeddel, Mabruka Zletni, Nicolino Ruperto, Alberto Martini, Randy Q Cron, Angelo Ravelli
OBJECTIVE: To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH-2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)-associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection. METHODS: International pediatric rheumatologists and hemato-oncologists were asked to retrospectively collect clinical information from patients with systemic JIA-associated MAS and confusable conditions...
October 2014: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/24839206/randomized-double-blind-placebo-controlled-trial-of-the-efficacy-and-safety-of-rilonacept-in-the-treatment-of-systemic-juvenile-idiopathic-arthritis
#15
RANDOMIZED CONTROLLED TRIAL
Norman T Ilowite, Kristi Prather, Yuliya Lokhnygina, Laura E Schanberg, Melissa Elder, Diana Milojevic, James W Verbsky, Steven J Spalding, Yukiko Kimura, Lisa F Imundo, Marilynn G Punaro, David D Sherry, Stacey E Tarvin, Lawrence S Zemel, James D Birmingham, Beth S Gottlieb, Michael L Miller, Kathleen O'Neil, Natasha M Ruth, Carol A Wallace, Nora G Singer, Christy I Sandborg
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...
September 2014: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/24786928/clinically-inactive-disease-in-a-cohort-of-children-with-new-onset-polyarticular-juvenile-idiopathic-arthritis-treated-with-early-aggressive-therapy-time-to-achievement-total-duration-and-predictors
#16
RANDOMIZED CONTROLLED TRIAL
Carol A Wallace, Edward H Giannini, Steven J Spalding, Philip J Hashkes, Kathleen M O'Neil, Andrew S Zeft, Ilona S Szer, Sarah Ringold, Hermine I Brunner, Laura E Schanberg, Robert P Sundel, Diana S Milojevic, Marilynn G Punaro, Peter Chira, Beth S Gottlieb, Gloria C Higgins, Norman T Ilowite, Yukiko Kimura, Anne Johnson, Bin Huang, Daniel J Lovell
OBJECTIVE: To determine the elapsed time while receiving aggressive therapy to the first observation of clinically inactive disease (CID), total duration of CID and potential predictors of this response in a cohort of children with recent onset of polyarticular juvenile idiopathic arthritis (poly-JIA). METHODS: Eighty-five children were randomized blindly to methotrexate (MTX), etanercept, and rapidly tapered prednisolone (MEP) or MTX monotherapy and assessed for CID over 1 year of treatment...
June 2014: Journal of Rheumatology
https://www.readbyqxmd.com/read/24677982/a52-the-impact-of-adalimumab-on-growth-in-patients-with-juvenile-idiopathic-arthritis
#17
Daniel J Lovell, Nicola Ruperto, Katerina Jarosova, Dana Nemcova, Veronika Vargova, Hartmut Michels, Elizabeth Chalom, Norman Ilowite, Carine Wouters, Hermine Brunner, Hartmut Kupper, Edward Giannini, Alberto Martini
BACKGROUND/PURPOSE: Children with juvenile idiopathic arthritis (JIA) often exhibit growth impairments. Treatment with adalimumab (ADA) has been shown to be safe and effective in JIA patients (pts) when dosed every other week (eow) for up to 3 years, but the effect of ADA on growth is not known. The purpose of this post hoc analysis is to describe growth parameters in pts with JIA treated with ADA in a clinical trial setting. METHODS: Pts aged 4-17 with polyarticular course JIA were enrolled in a phase 3, randomized-withdrawal, double-blind (DB), stratified, parallel-group study, which consisted of a 16-wk open-label (OL) lead-in phase, a 32-wk DB phase, and an OL extension (OLE) phase...
March 2014: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/24677923/a167-variations-in-patterns-of-care-across-pediatric-rheumatic-diseases-in-the-childhood-arthritis-rheumatology-alliance-network-registry
#18
Marc D Natter, Mei-Sing Ong, Norman T Ilowite, Kenneth D Mandl, Kelly L Mieszkalski, Christy I Sandborg, Carol Wallace, Laura E Schanberg
BACKGROUND/PURPOSE: In 2009, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) established a longitudinal multi-center, multiple disease U.S. national registry (CARRA Registry) for pediatric rheumatology with the intent of providing a new framework to drive observational clinical research and best practices, evidence-based care. Simultaneously, recognizing that widely variable therapeutic approaches hinder the ability to conduct meaningful comparative effectiveness studies and pragmatic trials in pediatric rheumatic diseases, CARRA investigators convened expert groups to formulate new consensus-based treatment plans (CTPs) in 5 major pediatric rheumatic disease areas...
March 2014: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/24677915/a160-role-of-interleukin-1-in-abnormal-monocyte-phenotype-in-systemic-onset-juvenile-idiopathic-arthritis
#19
Yujuan Zhang, Claudia Macaubas, Saloni Gupta, Clarissa Klein, Virginia Pascual, Arielle Hay, Susan D Thompson, Christy I Sandborg, Norman T Ilowite, Elizabeth D Mellins
BACKGROUND/PURPOSE: Monocytes phenotype changes in different microenvironments: the proinflammatory M1, regulatory M2, and M2-like phenotypes are each regulated by specific transcriptional factors (TFs). We have observed altered phenotypes in blood monocytes in systemic onset juvenile idiopathic arthritis (sJIA), including a decreased M1 cells, an increased mixed M1/M2 cells, and reduced secretion of IL-1, despite an increased IL-1b response to LPS (PMID 22281427). Here, we investigate whether these monocyte phenotypes are affected by IL-1 blockade...
March 2014: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/24144710/using-registries-to-identify-adverse-events-in-rheumatic-diseases
#20
REVIEW
Geraldina Lionetti, Yukiko Kimura, Laura E Schanberg, Timothy Beukelman, Carol A Wallace, Norman T Ilowite, Jane Winsor, Kathleen Fox, Marc Natter, John S Sundy, Eric Brodsky, Jeffrey R Curtis, Vincent Del Gaizo, Solomon Iyasu, Angelika Jahreis, Ann Meeker-O'Connell, Barbara B Mittleman, Bernard M Murphy, Eric D Peterson, Sandra C Raymond, Soko Setoguchi, Jeffrey N Siegel, Rachel E Sobel, Daniel Solomon, Taunton R Southwood, Richard Vesely, Patience H White, Nico M Wulffraat, Christy I Sandborg
The proven effectiveness of biologics and other immunomodulatory products in inflammatory rheumatic diseases has resulted in their widespread use as well as reports of potential short- and long-term complications such as infection and malignancy. These complications are especially worrisome in children who often have serial exposures to multiple immunomodulatory products. Post-marketing surveillance of immunomodulatory products in juvenile idiopathic arthritis (JIA) and pediatric systemic lupus erythematosus is currently based on product-specific registries and passive surveillance, which may not accurately reflect the safety risks for children owing to low numbers, poor long-term retention, and inadequate comparators...
November 2013: Pediatrics
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