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https://www.readbyqxmd.com/read/28633612/clinical-features-and-treatment-outcomes-in-large-granular-lymphocytic-leukemia-lgll
#1
Srinivasa R Sanikommu, Michael J Clemente, Peter Chomczynski, Manuel G Afable, Andres Jerez, Swapna Thota, Bhumika Patel, Cassandra Hirsch, Aziz Nazha, John Desamito, Alan Lichtin, Brad Pohlman, Mikkael A Sekeres, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Large granular lymphocytic leukemia (LGLL) represents a clonal/oligoclonal lymphoproliferation of cytotoxic T and natural killer cells often associated with STAT3 mutations. When symptomatic, due to mostly anemia and neutropenia, therapy choices are often empirically-based, because only few clinical trials and systematic studies have been performed. Incorporating new molecular and flow cytometry parameters, we identified 204 patients fulfilling uniform criteria for LGLL diagnoses and analyzed clinical course with median follow-up of 36 months, including responses to treatments...
June 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28612180/immunogenicity-of-biologics-in-chronic-inflammatory-diseases-a-systematic-review
#2
REVIEW
Vibeke Strand, Alejandro Balsa, Jamal Al-Saleh, Leonor Barile-Fabris, Takahiko Horiuchi, Tsutomu Takeuchi, Sadiq Lula, Charles Hawes, Blerina Kola, Lisa Marshall
OBJECTIVES: A systematic review was conducted to explore the immunogenicity of biologic agents across inflammatory diseases and its potential impact on efficacy/safety. METHODS: Literature searches were conducted through November 2016 to identify controlled and observational studies of biologics/biosimilars administered for treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), psoriasis (Ps), Crohn's disease, and ulcerative colitis...
June 13, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28611475/murine-lrba-deficiency-causes-ctla-4-deficiency-in-tregs-without-progression-to-immune-dysregulation
#3
Deborah Burnett, Ian Parish, Etienne Masle-Farquhar, Robert Brink, Christopher Goodnow
Inherited mutations in Lipopolysaccharide Responsive Beige-like Anchor (LRBA) cause a recessive human immune dysregulation syndrome with memory B cell and antibody deficiency (common variable immunodeficiency, CVID), inflammatory bowel disease, enlarged spleen and lymph nodes, accumulation of activated T cells, and multiple autoimmune diseases. To understand the pathogenesis of the syndrome, C57BL/6 mice carrying a homozygous truncating mutation in Lrba were produced using CRISPR/Cas9-mediated gene targeting...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28610606/biologic-therapies-for-refractory-juvenile-dermatomyositis-five-years-of-experience-of-the-childhood-arthritis-and-rheumatology-research-alliance-in-north-america
#4
C H Spencer, K Rouster-Stevens, H Gewanter, G Syverson, R Modica, K Schmidt, H Emery, C Wallace, S Grevich, K Nanda, Y D Zhao, S Shenoi, S Tarvin, S Hong, C Lindsley, J E Weiss, M Passo, K Ede, A Brown, K Ardalan, W Bernal, M L Stoll, B Lang, R Carrasco, C Agaiar, L Feller, H Bukulmez, R Vehe, H Kim, H Schmeling, D Gerstbacher, M Hoeltzel, B Eberhard, R Sundel, S Kim, A M Huber, A Patwardhan
BACKGROUND: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA)...
June 13, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/28608166/abatacept-a-review-in-rheumatoid-arthritis
#5
Hannah A Blair, Emma D Deeks
The biological DMARD (bDMARD) abatacept (Orencia(®)), a recombinant fusion protein, selectively modulates a co-stimulatory signal necessary for T-cell activation. In the EU, abatacept is approved for use in patients with highly active and progressive rheumatoid arthritis (RA) not previously treated with methotrexate. Abatacept is also approved for the treatment of moderate to severe active RA in patients with an inadequate response to previous therapy with at least one conventional DMARD (cDMARD), including methotrexate or a TNF inhibitor...
June 12, 2017: Drugs
https://www.readbyqxmd.com/read/28598787/severe-adverse-drug-reactions-to-biological-disease-modifying-anti-rheumatic-drugs-in-elderly-patients-with-rheumatoid-arthritis-in-clinical-practice
#6
Leticia Leon, Alejandro Gomez, Cristina Vadillo, Esperanza Pato, Luis Rodriguez-Rodriguez, Juan Angel Jover, Lydia Abasolo
OBJECTIVES: Biological DMARDs are widely used in the treatment of rheumatoid arthritis (RA) but their relationship with adverse drug reaction (ADR) is important. RA is now known to increase in incidence and prevalence with age. Our objective was to assess the incidence of severe ADR in the long term, compare safety between the different bDMARDs and identify other possible risk factors for severe ADR in elderly RA patients. METHODS: A 14-year retrospective longitudinal study was performed...
June 6, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28594905/comparative-risk-of-hospitalized-infection-between-biological-agents-in-rheumatoid-arthritis-patients-a-multicenter-retrospective-cohort-study-in-japan
#7
Shunsuke Mori, Tamami Yoshitama, Toshihiko Hidaka, Fumikazu Sakai, Mizue Hasegawa, Yayoi Hashiba, Eiichi Suematsu, Hiroshi Tatsukawa, Akinari Mizokami, Shigeru Yoshizawa, Naoyuki Hirakata, Yukitaka Ueki
OBJECTIVE: Knowing the risk of hospitalized infection associated with individual biological agents is an important factor in selecting the best treatment option for patients with rheumatoid arthritis (RA). This study examined the comparative risk of hospitalized infection between biological agents in a routine care setting. METHODS: We used data for all RA patients who had first begun biological therapy at rheumatology divisions of participating community hospitals in Japan between January 2009 and December 2014...
2017: PloS One
https://www.readbyqxmd.com/read/28581446/tregs-restrain-dendritic-cell-autophagy-to-ameliorate-autoimmunity
#8
Themis Alissafi, Aggelos Banos, Louis Boon, Tim Sparwasser, Alessandra Ghigo, Kajsa Wing, Dimitrios Vassilopoulos, Dimitrios Boumpas, Triantafyllos Chavakis, Ken Cadwell, Panayotis Verginis
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte-associated protein 4-dependent (CTLA4-dependent) manner...
June 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28572054/targeting-the-programmed-cell-death-1-pathway-in-rheumatoid-arthritis
#9
REVIEW
Sabina Sandigursky, Gregg J Silverman, Adam Mor
Since the introduction of TNF-α inhibitors and other biologic agents, the clinical outcome for many treated rheumatoid arthritis patients has significantly improved. However, there are still a substantial proportion of patients that are intolerant, or have inadequate responses, with current agents that have become the standards of care. While the majority of these agents are designed to affect the inflammatory features of the disease, there are also agents in the clinic that instead target lymphocyte subsets (e...
May 29, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28570568/the-risk-of-tuberculosis-disease-in-rheumatoid-arthritis-patients-on-biologics-and-targeted-therapy-a-15-year-real-world-experience-in-taiwan
#10
Chong Hong Lim, Hsin-Hua Chen, Yi-Hsing Chen, Der-Yuan Chen, Wen-Nan Huang, Jaw-Ji Tsai, Tsu-Yi Hsieh, Chia-Wei Hsieh, Wei-Ting Hung, Ching-Tsai Lin, Kuo-Lung Lai, Kuo-Tung Tang, Chih-Wei Tseng, Yi-Ming Chen
The objective of this study is to determine the risk of tuberculosis (TB) disease in biologics users among rheumatoid arthritis (RA) patients in Taiwan from 2000 to 2015. This retrospective cohort study enrolled adult RA patients initiated on first biologics at Taichung Veterans General Hospital. TB risks were determined as hazard ratio (HR) with 95% confidence interval (CI) using cox regression. A total of 951 patients were recruited; etanercept (n = 443), adalimumab (n = 332), abatacept (n = 74), golimumab (n = 60), tocilizumab (n = 31) and tofacitinib (n = 11)...
2017: PloS One
https://www.readbyqxmd.com/read/28564491/abatacept-attenuates-t-follicular-helper-cell-dependent-b-cell-hyperactivity-in-primary-sj%C3%A3-gren-s-syndrome
#11
Gwenny M Verstappen, Petra M Meiners, Odilia B J Corneth, Annie Visser, Suzanne Arends, Wayel H Abdulahad, Rudi W Hendriks, Arjan Vissink, Frans G M Kroese, Hendrika Bootsma
Objective To assess the effect of abatacept (CTLA-4-Ig), which limits T-cell activation, on homeostasis of CD4(+) T-cell subsets and T-cell-dependent B-cell hyperactivity in patients with primary Sjögren's syndrome (pSS). Methods Fifteen pSS patients treated with abatacept were included. Circulating CD4(+) T-cell and B-cell subsets were analyzed by flow cytometry at baseline, on treatment and off treatment. CD4(+) effector T-cell subsets and T regulatory (Treg)-cells were identified based on expression of CD45RA, CXCR3, CCR6, CCR4, CXCR5, programmed death-1 (PD-1), inducible costimulator (ICOS) and FoxP3...
May 31, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28560470/cost-per-response-for-abatacept-versus-adalimumab-in-rheumatoid-arthritis-by-acpa-subgroups-in-germany-italy-spain-us-and-canada
#12
Laure Weijers, Christoph Baerwald, Francesco S Mennini, José M Rodríguez-Heredia, Martin J Bergman, Denis Choquette, Kirsten H Herrmann, Giulia Attinà, Carmela Nappi, Silvia Jimenez Merino, Chad Patel, Mondher Mtibaa, Jason Foo
Rheumatoid arthritis (RA) is a chronic inflammatory disorder leading to disability and reduced quality of life. Effective treatment with biologic DMARDs poses a significant economic burden. The Abatacept versus Adalimumab Comparison in Biologic-Naïve RA Subjects with Background Methotrexate (AMPLE) trial was a head-to-head, randomized study comparing abatacept in serum anti-citrullinated protein antibody (ACPA)-positive patients, with increasing efficacy across ACPA quartile levels. The aim of this study was to evaluate the cost per response accrued using abatacept versus adalimumab in ACPA-positive and ACPA-negative patients with RA from the health care perspective in Germany, Italy, Spain, the US and Canada...
May 30, 2017: Rheumatology International
https://www.readbyqxmd.com/read/28550592/certolizumab-pegol-for-treating-rheumatoid-arthritis-following-inadequate-response-to-a-tnf-%C3%AE-inhibitor-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#13
REVIEW
Iñigo Bermejo, Matt Stevenson, Rachel Archer, John W Stevens, Edward Goka, Mark Clowes, David L Scott, Adam Young
As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (UCB Pharma) of certolizumab pegol (CZP; Cimzia(®)) to submit evidence of its clinical and cost effectiveness for the treatment of rheumatoid arthritis (RA) following inadequate response to a tumour necrosis factor-α inhibitor (TNFi). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
May 26, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28545554/whipple-s-disease-mimicking-rheumatoid-arthritis-can-cause-misdiagnosis-and-treatment-failure
#14
Cornelia Glaser, Siegbert Rieg, Thorsten Wiech, Christine Scholz, Dominique Endres, Oliver Stich, Peter Hasselblatt, Walter Geißdörfer, Christian Bogdan, Annerose Serr, Georg Häcker, Reinhard E Voll, Jens Thiel, Nils Venhoff
BACKGROUND: Whipple's disease, a rare chronic infectious disorder caused by Tropheryma whipplei, may present with predominant joint manifestations mimicking rheumatoid arthritis (RA). METHODS: A retrospective single-center cohort study of seven patients was performed. Clinical symptoms were assessed by review of medical charts and Whipple's disease was diagnosed by periodic-acid-Schiff-stain and/or Tropheryma whipplei-specific polymerase-chain-reaction. RESULTS: Median age at disease onset was 54 years, six patients were male...
May 25, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28545499/pre-silencing-of-genes-involved-in-the-electron-transport-chain-etc-pathway-is-associated-with-responsiveness-to-abatacept-in-rheumatoid-arthritis
#15
C Derambure, G Dzangue-Tchoupou, C Berard, N Vergne, M Hiron, M A D'Agostino, P Musette, O Vittecoq, T Lequerré
BACKGROUND: In the current context of personalized medicine, one of the major challenges in the management of rheumatoid arthritis (RA) is to identify biomarkers that predict drug responsiveness. From the European APPRAISE trial, our main objective was to identify a gene expression profile associated with responsiveness to abatacept (ABA) + methotrexate (MTX) and to understand the involvement of this signature in the pathophysiology of RA. METHODS: Whole human genome microarrays (4 × 44 K) were performed from a first subset of 36 patients with RA...
May 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28541295/spondyloarthropathies-abatacept-treatment-for-psa
#16
Dario Ummarino
No abstract text is available yet for this article.
July 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28525959/challenges-and-opportunities-in-targeting-the-cd28-ctla-4-pathway-in-transplantation-and-autoimmunity
#17
Rebecca L Crepeau, Mandy L Ford
T cell activation is a complex process that requires multiple cell signaling pathways, including a primary recognition signal and additional costimulatory signals. One of the best-characterized costimulatory pathways includes the Ig superfamily members CD28 and CTLA-4 and their ligands CD80 and CD86. Areas covered: This review discusses past, current and future biological therapies that have been utilized to block the CD28/CTLA-4 cosignaling pathway in the settings of autoimmunity and transplantation, as well the challenges facing successful implementation of these therapies...
May 30, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28516880/abatacept-therapy-reduces-cd28-cxcr5-follicular-helper-like-t-cells-in-patients-with-rheumatoid-arthritis
#18
Shunsuke Fukuyo, Shingo Nakayamada, Shigeru Iwata, Satoshi Kubo, Kazuyoshi Saito, Yoshiya Tanaka
OBJECTIVES: The characteristics of T cells targeted by abatacept (ABT) in cases of rheumatoid arthritis (RA) are still unknown. The goal of the study was to determine the pathogenicity of T cells and the predictors of therapeutic effects of ABT. METHODS: We analysed the peripheral T cell phenotype of 34 RA patients via flow cytometry. The correlation of the phenotypes of CD4+ T cells with clinical disease activity and change in CD4+ T cell subsets at baseline and 24 weeks after ABT treatment were evaluated...
April 27, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28511719/interleukin-10-producing-lag3-regulatory-t-cells-are-associated-with-disease-activity-and-abatacept-treatment-in-rheumatoid-arthritis
#19
Shinichiro Nakachi, Shuji Sumitomo, Yumi Tsuchida, Haruka Tsuchiya, Masanori Kono, Rika Kato, Keiichi Sakurai, Norio Hanata, Yasuo Nagafuchi, Shoko Tateishi, Hiroko Kanda, Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
BACKGROUND: Regulatory T cells (Tregs) play a role in the suppression of inflammation in autoimmune diseases, and lymphocyte activation gene 3 (LAG3) was reported as a marker of interleukin (IL)-10-producing Tregs. We aimed to clarify the function of human IL-10-producing CD4(+)CD25(-)LAG3(+) T cells (LAG3(+) Tregs) and their association with rheumatoid arthritis (RA). METHODS: LAG3(+) Tregs of human peripheral blood mononuclear cells (PBMCs) were cultured with B cells and follicular helper T cells to examine antibody suppression effects...
May 16, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28507894/re-administration-of-abatacept-for-the-control-of-articular-symptoms-of-rheumatoid-arthritis-during-anti-tuberculous-therapy
#20
Hironori Kawamoto, Jin Takasaki, Satoru Ishii, Manabu Suzuki, Eriko Morino, Go Naka, Motoyasu Iikura, Shinyu Izumi, Yuichiro Takeda, Haruhito Sugiyama
This case report describes the re-administration of abatacept to successfully reduce the articularsymptoms of a patient with rheumatoid arthritisduring the intensive phase of anti-tuberculous therapy. A 75-year-old man developed active pulmonary tuberculosis during the administration of abatacept for rheumatoid arthritis. The patient experienced a paradoxical reaction and exacerbation of rheumatoid arthritis that caused us to discontinue the abatacept. Later re-administration of abatacept along with anti-tuberculosis treatment led to well-controlled rheumatoid arthritis without exacerbation of the tuberculosis...
2017: Respiratory Medicine Case Reports
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