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炎症性肠病的诊疗进展-10-30
~ 10 % Budesonide Liver ~ 90 % metabolism in the liver Budesonide enema CA/03/85 BUDESONIDE-METABOLISM AFTER RECTAL APPLICATION Brattsand, 1990 CDT/03/62 BUDESONIDE (pH-DEPENDENT) vs PREDNISONE IN ACTIVE CD Bar Meir, AGA 1998 8 weeks BUD, 3 x 3 mg Pred. (40 mg, (ITT/PP) 30 mg, 5 mg taper) (n = 100) (n = 101) Remission (%) 51.0/56.0 52.5/55.2 Remission without SE (%) 30.0/33.3 13.9/13.8 * SE (n) ** 39 80 * p = 0.004 ** Moon face, acne, buffalo hump, hirsutism CDT/04/16 AZATHIOPRINE IN ACTIVE CROHN′S DISEASE – SHORT AND LONG-TERM EFFECTS Candy, 1995 Prednisolone (12 weeks, tapered) + + Placebo Azathioprine, 2.5 mg/kg (n = 30) (n = 33) Remission 12 weeks (%) 63 73 Remission 15 months (%) 7 42 * * = significant From 12 weeks on only AZA! CDT/03/03 INFLUENCE OF SMOKING ON THE COURSE OF CD - INTERVENTION STUDY months after inclusion risk of a flare (%) ex-smokers (n = 59) smokers (n = 59) non-smokers (n = 59) Cosnes, 2001 WHY DO WE NEED NEW TREATMENTS FOR IBD? CA/02/16 Life expectancy normalized, social integration preserved 90 %, acute disease treated effectively in most cases Problems: - Some refractory and more steroid dependent cases - Side effects of steroids and other drugs - High relapse rate in 50 % of patients - No mucosal healing Healing and normal life quality are predominant goals ! Immune Interventional Therapy for IBD Ag Presentation T Cells TH Cells Mast Cells Macrophages B Cells IL2 IFNg O2- CYCLOSPORINE ANTI- METABOLITES O2- SCAVENGERS INHIBITORS HYDROXY- CHLOROQUINE Therapeutic Uses of Monoclonal Antibodies Antibodies can be designed to target any substance that is immunogenic Enzymes Cellular structure Proteins Antibody Neutralization of TNF-? TNF TNF TNF-AB cAMP IL-10 Thalidomide Metalloproteinase inhibitor TNF-Trimer TNF-AB Apoptosis TNF CA/03/42 EFFECTS OF ANTI TNF-STRATEGIES Healing of Coloni
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