The rationale for the current boom in anti-TNFalpha treatment. Is there an effective means to define therapeutic targets for drugs that provide all the benefits of anti-TNFalpha and minimise hazards?

Abstract:

:Progress in understanding mechanisms of disease are necessary to usher in major changes in treatment. A new era in rheumatoid arthritis (RA) and related chronic autoimmune/inflammatory diseases is now beginning, with a variety of anti-TNFalpha treatments licensed for use in both RA and Crohn's disease. The rationale for this new treatment lies in an understanding that cytokines are critical, rate limiting molecules lying at the heart of the chronic autoimmune/inflammatory disease process. This understanding was developed from the critical evaluation of a hypothesis that was proposed linking cytokines, antigen presentation and autoimmunity in 1983. Detailed analysis focusing on the major site of the disease, the rheumatoid synovium was essential to developing indications that blockade of TNFalpha might be efficacious. This clue was validated using anti-TNFalpha treatment of an animal model of RA, murine collagen induced arthritis, and by immunohistochemical demonstration of upregulated TNF and TNF-R expression in the synovium. With this three pronged rationale, the authors were able to convince Centocor, Inc, which had developed a chimaeric anti-TNFalpha antibody for use in sepsis, to work with them to test the concept that TNFalpha blockade would be beneficial in RA. With the success of that first trial, other companies have subsequently tested their anti-TNF strategies successfully. Current interests extend to understanding the processes that regulate TNF production in the rheumatoid joint. Progress in this area is discussed, using adenoviruses to infect normal macrophages and rheumatoid synovium.

journal_name

Ann Rheum Dis

authors

Feldmann M,Bondeson J,Brennan FM,Foxwell BM,Maini RN

doi

10.1136/ard.58.2008.i27

subject

Has Abstract

pub_date

1999-11-01 00:00:00

pages

I27-31

eissn

0003-4967

issn

1468-2060

journal_volume

58 Suppl 1

pub_type

杂志文章,评审
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    doi:10.1136/ard.2003.015453

    authors: Danieli MG,Cappelli M,Malcangi G,Logullo F,Salvi A,Danieli G

    更新日期:2004-12-01 00:00:00

  • Attempt to classify patients with arthritis of the hip suitable for prosthetic replacement, and their femoral heads.

    abstract::Using clinical, radiological, and morbid anatomical data about patients with arthritis of the hip and their femoral heads resected during total hip replacement, an attempt has been made first, to classify patients and femoral heads by a cluster analysis technique, and secondly and more realistically, to use existing c...

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    doi:10.1136/ard.34.4.298

    authors: Byers PD,Roper BA,Glennie B

    更新日期:1975-08-01 00:00:00

  • Factors in resistance to and recovery from M. pulmonis-induced arthritis in mice.

    abstract::A previous infection of C3H mice with viable Mycoplasma pulmonis organisms protected them from arthritis induced by intravenous inoculation of these organisms, whether or not their initial arthritis had resolved at the time of challenge. Although spleen cells obtained from such animals conferred resistance to acute ar...

    journal_title:Annals of the rheumatic diseases

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    doi:10.1136/ard.36.3.232

    authors: Taylor G,Taylor-Robinson D

    更新日期:1977-06-01 00:00:00

  • Efficacy of tumour necrosis factor blockers in reducing uveitis flares in patients with spondylarthropathy: a retrospective study.

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    journal_title:Annals of the rheumatic diseases

    pub_type: 临床试验,杂志文章

    doi:10.1136/ard.2006.052092

    authors: Guignard S,Gossec L,Salliot C,Ruyssen-Witrand A,Luc M,Duclos M,Dougados M

    更新日期:2006-12-01 00:00:00

  • Reactive arthritis after an outbreak of Yersinia pseudotuberculosis serotype O:3 infection.

    abstract:OBJECTIVE:To determine the occurrence and clinical characteristics of reactive arthritis (ReA) after an outbreak of Yersinia pseudotuberculosis serotype O:3 infection. METHODS:From 15 October to 6 November 1998, a widespread outbreak of Y pseudotuberculosis serotype O:3 occurred in Finland. A questionnaire on musculos...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,评审

    doi:10.1136/ard.62.9.866

    authors: Hannu T,Mattila L,Nuorti JP,Ruutu P,Mikkola J,Siitonen A,Leirisalo-Repo M

    更新日期:2003-09-01 00:00:00

  • Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-α, in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study.

    abstract:OBJECTIVE:To evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles of mavrilimumab, a human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, in subjects with rheumatoid arthritis (RA). METHODS:A randomised, double-blind, placebo-controlled, dose-e...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,随机对照试验

    doi:10.1136/ard.2010.146225

    authors: Burmester GR,Feist E,Sleeman MA,Wang B,White B,Magrini F

    更新日期:2011-09-01 00:00:00

  • Circulating levels of sialic acid and glycosaminoglycans: a diagnostic test for ankylosing spondylitis.

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.47.10.833

    authors: Susheela AK,Das TK,Khurana JS,Jayaswal A,Dave PK

    更新日期:1988-10-01 00:00:00

  • Endothelial cell cytotoxicity in inflammatory vascular diseases--the possible role of oxidised lipoproteins.

    abstract::One of the proposed mechanisms of vascular damage in connective tissue disease is the direct action of a cytotoxic serum factor inducing endothelial cell damage. The nature of this serum factor is unclear, but has been suggested to be a lipoprotein. Sera from patients with (1) systemic necrotising arteritis (polyarter...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.44.3.176

    authors: Blake DR,Winyard P,Scott DG,Brailsford S,Blann A,Lunec J

    更新日期:1985-03-01 00:00:00

  • A six year prospective study of a cohort of patients with fibromyalgia.

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.61.7.644

    authors: Baumgartner E,Finckh A,Cedraschi C,Vischer TL

    更新日期:2002-07-01 00:00:00

  • Co-activation of synovial fibroblasts by laminin-111 and transforming growth factor-beta induces expression of matrix metalloproteinases 3 and 10 independently of nuclear factor-kappaB.

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.2007.073809

    authors: Warstat K,Pap T,Klein G,Gay S,Aicher WK

    更新日期:2008-04-01 00:00:00

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,随机对照试验

    doi:10.1136/annrheumdis-2019-215163

    authors: Tanaka Y,Takeuchi T,Tanaka S,Kawakami A,Iwasaki M,Song YW,Chen YH,Wei JC,Lee SH,Rokuda M,Izutsu H,Ushijima S,Kaneko Y,Akazawa R,Shiomi T,Yamada E

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  • Autonomic neuropathy in systemic sclerosis: a case report and evaluation of six patients.

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.45.11.957

    authors: Sonnex C,Paice E,White AG

    更新日期:1986-11-01 00:00:00

  • Efficacy and safety of monotherapy with sirukumab compared with adalimumab monotherapy in biologic-naïve patients with active rheumatoid arthritis (SIRROUND-H): a randomised, double-blind, parallel-group, multinational, 52-week, phase 3 study.

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1136/annrheumdis-2017-212496

    authors: Taylor PC,Schiff MH,Wang Q,Jiang Y,Zhuang Y,Kurrasch R,Daga S,Rao R,Tak PP,Hsu B

    更新日期:2018-05-01 00:00:00

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1136/annrheumdis-2017-212878

    authors: Charles P,Terrier B,Perrodeau É,Cohen P,Faguer S,Huart A,Hamidou M,Agard C,Bonnotte B,Samson M,Karras A,Jourde-Chiche N,Lifermann F,Gobert P,Hanrotel-Saliou C,Godmer P,Martin-Silva N,Pugnet G,Matignon M,Aumaitre O,

    更新日期:2018-08-01 00:00:00

  • Patients with systemic lupus erythematosus, myositis, rheumatoid arthritis and scleroderma share activation of a common type I interferon pathway.

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,多中心研究

    doi:10.1136/ard.2011.150326

    authors: Higgs BW,Liu Z,White B,Zhu W,White WI,Morehouse C,Brohawn P,Kiener PA,Richman L,Fiorentino D,Greenberg SA,Jallal B,Yao Y

    更新日期:2011-11-01 00:00:00

  • Radiographic assessment of patellofemoral osteoarthritis.

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.52.9.655

    authors: Jones AC,Ledingham J,McAlindon T,Regan M,Hart D,MacMillan PJ,Doherty M

    更新日期:1993-09-01 00:00:00

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/annrheumdis-2019-216155

    authors: Adamichou C,Nikolopoulos D,Genitsaridi I,Bortoluzzi A,Fanouriakis A,Papastefanakis E,Kalogiannaki E,Gergianaki I,Sidiropoulos P,Boumpas DT,Bertsias GK

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  • Immunopathogenesis of Libman-Sacks endocarditis. Assessment by light and immunofluorescent microscopy in two patients.

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.36.6.508

    authors: Shapiro RF,Gamble CN,Wiesner KB,Castles JJ,Wolf AW,Hurley EJ,Salel AF

    更新日期:1977-12-01 00:00:00

  • Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry.

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,多中心研究

    doi:10.1136/ard.2010.137422

    authors: Salmon-Ceron D,Tubach F,Lortholary O,Chosidow O,Bretagne S,Nicolas N,Cuillerier E,Fautrel B,Michelet C,Morel J,Puéchal X,Wendling D,Lemann M,Ravaud P,Mariette X,RATIO group.

    更新日期:2011-04-01 00:00:00

  • Mixed connective tissue disease associated with autoimmune hepatitis and thyroiditis.

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.51.4.544

    authors: Tomsic M,Ferlan-Marolt V,Kveder T,Hojker S,Rozman B

    更新日期:1992-04-01 00:00:00

  • Gastrin, gastric acid secretion, and gastric microflora in patients with rheumatoid arthritis.

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.45.6.475

    authors: Henriksson K,Uvnäs-Moberg K,Nord CE,Johansson C,Gullberg R

    更新日期:1986-06-01 00:00:00

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.46.3.244

    authors: Englert HJ,Hughes GR,Walport MJ

    更新日期:1987-03-01 00:00:00

  • Beta 2 microglobulin measurements in saliva of patients with primary Sjögren's syndrome: influence of flow.

    abstract:OBJECTIVES:To determine the diagnostic value of beta 2 microglobulin in parotid saliva, its concentration in relation to salivary flow was determined in 29 patients with primary Sjögren's syndrome and in 30 normal controls. The specific secretion rate of beta 2 microglobulin was calculated. METHODS:Parotid saliva samp...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.52.6.461

    authors: van der Geest SA,Markusse HM,Swaak AJ

    更新日期:1993-06-01 00:00:00

  • Action of nonsteroidal, anti-inflammatory drugs on human and rat peripheral leucocyte migration in vitro.

    abstract::Using an in vitro system of cell migration from glass capillary tubes, the nonsteroidal, anti-inflammatory agents sodium salicylate, aspirin, ibuprofen, phenylbutazone, and indomethacin were shown to inhibit the migration of human peripheral leucocytes in a dose-related manner. This drug action was not confined to one...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.36.3.239

    authors: Brown KA,Collins AJ

    更新日期:1977-06-01 00:00:00

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    pub_type: 杂志文章

    doi:10.1136/ard.38.1.14

    authors: de Witte TJ,Geerdink PJ,Lamers CB,Boerbooms AM,van der Korst JK

    更新日期:1979-02-01 00:00:00

  • Anticentromere antibody in patients without CREST and scleroderma: association with active digital vasculitis, rheumatic and connective tissue disease.

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    pub_type: 杂志文章

    doi:10.1136/ard.48.9.771

    authors: Goldman JA

    更新日期:1989-09-01 00:00:00

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    abstract:OBJECTIVE:To investigate the predictive value of discordance between (1) tender and swollen joint count and (2) patient's and evaluator's global assessment on remission in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS:From the prospective, multicentre Norwegian-Disease-Modifying Antirh...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,多中心研究

    doi:10.1136/annrheumdis-2016-210283

    authors: Michelsen B,Kristianslund EK,Hammer HB,Fagerli KM,Lie E,Wierød A,Kalstad S,Rødevand E,Krøll F,Haugeberg G,Kvien TK

    更新日期:2017-04-01 00:00:00

  • How long should we talk to patients? A study in doctor-patient communication.

    abstract::The 13 questions to which 173 rheumatic outpatients most frequently wished to know the answer were made the basis of a structured interview. Two lengths of interview were conducted in a controlled trial (short being of 2 minutes' duration, long ranging from 4 to 11 minutes). Sixty patients referred directly from their...

    journal_title:Annals of the rheumatic diseases

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1136/ard.41.3.250

    authors: Wright V,Hopkins R,Burton K

    更新日期:1982-06-01 00:00:00

  • Haemophilus influenzae tenosynovitis.

    abstract::A case is reported of polytenosynovitis in a 31-year-old male during the course of a severe bacteraemic illness caused by Haemophilus influenzae type b. The clinical presentation was similar to tenosynovitis caused by bacterial or viral agents. As the management of the H. influenzae tenosynovitis would differ from tha...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.38.6.561

    authors: Bansal S,Magnussen CR,Napodano RJ

    更新日期:1979-12-01 00:00:00

  • The PTPN22*C1858T functional polymorphism is associated with susceptibility to inflammatory polyarthritis but neither this nor other variants spanning the gene is associated with disease outcome.

    abstract:BACKGROUND:The PTPN22 gene has been widely confirmed as a susceptibility gene for rheumatoid arthritis (RA) in populations of Northern European descent. The aim of the current study was to explore the role of variants spanning the PTPN22 gene in determining susceptibility to and outcome of inflammatory polyarthritis (I...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.2007.071894

    authors: Naseem H,Thomson W,Silman A,Worthington J,Symmons D,Barton A

    更新日期:2008-02-01 00:00:00