Rheumatoid Arthritis		Infliximab
Rhumatoid Arthritis		Remicade

Pictures

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Infliximab REMICADE® is an anti inflammatory monoclonal antibody for the treatment of Crohn s disease and rheumatoid arthritis which is licensed from Centocor

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oder das Binden von Schnürsenkeln nicht mehr allein ausgeführt werden Massive Behinderungen bis hin zur Rollstuhlpflichtigkeit der Patienten sind möglich Neben der beschriebenen stetigen Verschlechterung kann die rheumatoide Arthritis aber auch schubförmig verlaufen Rheumaschübe sind Phasen der sehr akuten Entzündung

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Established rheumatoid arthritis not responding to any therapy consider etanercept Infliximab depending on availability References

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Figure 1 Kaplan Meier estimate of the proportion of patients who had not lost response through Week 54

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an infection including sepsis or tuberculosis you may be entitled to compensation Remicade Infliximab is an immune suppressing drug used to treat rheumatoid arthritis and Crohn s disease

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Our Rheumatoid Arthritis Program

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could be that it is depleting cells that express TNF alpha However at this moment we have no very good fix on how important that really is in vivo in patients with rheumatoid arthritis Slide Structure Damage = Erosions + Joint Space Narrowing JSN Now you heard from Dr Sharp that joint damage in rheumatoid arthritis as assessed by serial x rays of hands and feet where

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There are now some papers showing that infliximab used early in the disease can put patients in remission and they can then

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type IA receptors These are synoviocytes which make Rank ligand And so we certainly are able to say that the Rank ligand positive expected type of cell is present at the pannus junction Slide Infliximab Reduces Mediators of Pannus Formation in RA Patients And here we see from our biopsy studies before and after infliximab Remicade® how there is a marked reduction in CD3

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Combination drug therapy uses two or more DMARDs together this is cheaper than injections Injections Biological agents include Tumor necrosis factor TNFa blockers etanercept Enbrel infliximab Remicade adalimumab Humira Combination therapy uses two or more DMARDs together Corticosteroids may also

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there still is some concern about that death as anticipated and malignancies as compared to the predicted NCI database being about the same That was true at one year and also at two years Slide Summary of Efficacy So summary for Infliximab with methotrexate in patients with an inadequate response to methotrexate infliximab can be considered more effective than placebo in

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we would speculate that this complex pathway is being regulated by multiple steps of diminution in precursor cells cell damaging factors like Rank ligand produced by synoviocytes and T cells Slide Modulation of Serum MMP 1 and Total MMP 3 Levels Following Anti TNF alpha Infliximab Therapy Now have we any experimental observations to support these hypotheses Well we have some

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in the presence of free TNF or receptor in excess Moreover although this is an IgG1 construct when this receptor binds to cells that have TNF on their surface it doesn t lyse them Slide Remicade® Infliximab In contrast the molecule Remicade® which is a chimeric IgG1 monoclonal antibody also has high affinity but only for TNF alpha not for lymphotoxin and this

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in these two circulating proenzymes or inactivated enzymes giving us some reflection of the turnover of these enzymes that are so important in degrading both cartilage and bone matrix Slide BMPR Type IA Positive Cells arrows in RA Pannus Role in Osteoclastogenesis And here we have study in the current issue of Arthritis and Rheumatism showing the presence of these

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Slide Infliximab Methotrexate Combination ATTRACT Infliximab is the chimeric antibody to TNF It was studied in the anti TNFRA trial with concomitant therapy which included 428 patients

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of MMP 1 and MMP 13 is probably responsible for cartilage degradation But in addition TNF alpha has a profound effect on anabolic activity of chondrocytes so that new matrix is not made Slide TNF alpha and Bone Erosion in RA Copying or reproduction of this slide is prohibited without the writtenpermission of Prof R N Maini Kennedy Institute of Rheumatology

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Slide TNF Production Action or Neutralisation Copying or reproduction of this slide is prohibited without the writtenpermission of Prof R N Maini Kennedy Institute of Rheumatology

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Slide TNF Production Action or Neutralisation

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Slide Collagenases and Joint Destruction Now what about tissue damage Well when we think of cartilage tissue damage there are at least two or three different fronts simultaneously

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