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Transcript of Inflammatory Bowel Disease Treatment. Epidemiology Clinical Laboratory Imaging Pathology Response to...
![Page 1: Inflammatory Bowel Disease Treatment. Epidemiology Clinical Laboratory Imaging Pathology Response to treatment IBD.](https://reader035.fdocuments.in/reader035/viewer/2022062322/56649db05503460f94a9e03e/html5/thumbnails/1.jpg)
Inflammatory Bowel Disease Treatment
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Epidemiology
Clinical
Laboratory
Imaging
Pathology
Response to treatment
IBD
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GOALS OF THERAPY
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CONVENTIONAL DRUG THERAPIES
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ULCERATIVE COLITIS THERAPY
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CROHN’S DISEASE THERAPY
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Medications
5-Aminosalicylic acid
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SULFASALAZINE
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SULFASALAZINE METABOLISM
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AMINOSALICYLATES
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AMINOSALICYLATE DISTRIBUTION
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Sulfasalazine Versus 5-ASA Therapy
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Oral vs Combination 5-ASA Treatment in UC
Active Disease Maintenance
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Dose Response to Oral Mesalamine in Active
Crohn’s Disease
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5-aminosalicylate Versus Sulfasalazine Toxicity
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Medications
Antibiotics
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METRONIDAZOLE
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CIPROFLOXACIN AND METRONIDAZOLE VERSUS METHYLPREDNISOLONE IN ACTIVE CROHN’S DISEASE
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Medications
Corticosteroids
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STEROID PREPARATIONS
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SYSTEMIC CORTICOIDS
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TOPICAL CORTICOIDS
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RESULTS OF CORTICOSTEROID THERAPY
FOR CROHN’S DISEASE
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Ideal Anti-inflammatory Drug For Targeted Treatment Of IBD
• Delivery targeted to the inflammatory site
• Dissolves well in the lumen
• Extensive mucosal uptake, distribution and retention
• High intrinsic activity
• No local inactivation
• Extensive systemic (liver) inactivation
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Budesonide Pharmacology
• High topical potency
• High intrinsic activity
• Moderately high water solubility
• Affinity for glucocorticoid receptor – 200x hydrocortisone– 15x prednisolone
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Hypothalamic-Pituitary Adrenal Axis
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Oral Budesonide In Active Crohn’s Disease
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Oral Budesonide As Maintenance Therapy For
Crohn’s Disease
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Issues
• Post-surgery prevention• Steroid switching• Effect in children - growth etc• Side effects - bone• Quality of life• Activity in UC
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Medications
Immunomodulators
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AZATHIOPRINE AND 6-MERCAPTOPURINE
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6-mercaptopurine in Active Crohn’s Disease
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6-mercaptopurine and Azathioprine as
Maintenance Therapy in Crohn’s Disease
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6-mercaptopurine as Maintenance Therapy for
Ulcerative Colitis
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ADVERSE EFFECTS OF 6-MP/AZATHIOPRINE
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Methotrexate for Active Crohn’s Disease
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Methotrexate as Maintenance Therapy for
Crohn’s Disease
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Medications
Cyclosporine-A
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Cyclosporine in Active UC
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TOXICITY OF CYCLOSPORINE
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Medications
Biologicals Including Anti-TNF
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ANTIBODIES TO TNF
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Monoclonalantibody
No signal
Cytokine
Cytokine receptor
Choy EHS et al. Choy EHS et al. N Engl J Med.N Engl J Med. 2001;344:907–16. 2001;344:907–16.
Infliximab (Remicade)
• Chimeric IgG1 anti–TNF-α antibody
• Contains antigen-binding region of the mouse antibody and the constant region of the human antibody
• Binds to soluble and membrane-bound TNF- α with high affinity, impairing the binding of TNF- α to its receptor
• Kills cells that express TNF- α through antibody-dependent and complement-dependent cytotoxicity.
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INFLIXIMAB IN ACTIVE CROHN’S DISEASE
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INFLIXIMAB AS MAINTENANCE THERAPY FOR CROHN’S DISEASE
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INFLIXIMAB FOR FISTULIZING CROHN’S
DISEASE
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Anti-TNF for Active UC
• Moderate-to-severe ulcerative colitis
• Despite therapy with corticosteroids and/or immunomodulators
• Randomized to receive infliximab 5 mg/kg, 10 mg/kg, or placebo at O, 2w, 6w, and every 8 weeksACT 1 - 46wACT 2 - 30w
Rutgeerts et al. N Engl J Med 2005
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Rutgeerts et al. N Engl J Med, 2005
Anti-TNF for Maintenance in UC
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Infliximab as Rescue Therapy
• 45 fulminant or severe UC (Seo index)
• Day 0–3 colonoscopy - extent and severity of disease
• All patients IV steroids
• Day 4 to 8 if still severe colitis patients randomized to infliximab 5mg/kg /placebo
Janerot et al. Gastroenterology 2005
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Infliximab as Rescue TherapyResults
Janerot et al. Gastroenterology 2005
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ADVERSE EFFECTS OF INFLIXIMAB
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Medications
Emerging Treatments
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EMERGING TREATMENTS FOR IBD-2002
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TESTED UNCONVENTIONAL THERAPIES
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GUIDELINES FOR PREGNANCY
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NUTRITIONAL THERAPY IN IBD
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INDICATIONS FOR SURGERY IN ULCERATIVE COLITIS
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SURGICAL OPTIONS IN ULCERATIVE COLITIS
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ILEAL POUCH-ANAL ANASTOMOSIS
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LONG-TERM ADVERSE OUTCOMES OF ILEAL POUCH
ANAL ANASTOMOSIS
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POUCHITIS
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TREATMENT OPTIONS FOR POUCHITIS
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INDICATIONS FOR SURGERY IN CROHN’S DISEASE
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SURGICAL OPTIONS FOR INTRA-ABDOMINAL DISEASE
IN CROHN’S DISEASE
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STRICTUROPLASTY (HEINEKE-MIKULICZ)
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POST-OPERATIVE RECURRENCE RATES IN
CROHN’S DISEASE
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CROHN’S DISEASE POST-OPERATIVE PROPHYLAXIS
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MEDICAL TREATMENT OPTIONS FOR PERINEAL
DISEASE
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SURGICAL TREATMENT OPTIONS FOR PERINEAL
CROHN’S DISEASE
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THE DEAD SEA AND CROHN’S DISEASE –
Treatment of Fistuli