Inflammatory Bowel Disease Treatment. Epidemiology Clinical Laboratory Imaging Pathology Response to...
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Transcript of Inflammatory Bowel Disease Treatment. Epidemiology Clinical Laboratory Imaging Pathology Response to...
Inflammatory Bowel Disease Treatment
Epidemiology
Clinical
Laboratory
Imaging
Pathology
Response to treatment
IBD
GOALS OF THERAPY
CONVENTIONAL DRUG THERAPIES
ULCERATIVE COLITIS THERAPY
CROHN’S DISEASE THERAPY
Medications
5-Aminosalicylic acid
SULFASALAZINE
SULFASALAZINE METABOLISM
AMINOSALICYLATES
AMINOSALICYLATE DISTRIBUTION
Sulfasalazine Versus 5-ASA Therapy
Oral vs Combination 5-ASA Treatment in UC
Active Disease Maintenance
Dose Response to Oral Mesalamine in Active
Crohn’s Disease
5-aminosalicylate Versus Sulfasalazine Toxicity
Medications
Antibiotics
METRONIDAZOLE
CIPROFLOXACIN AND METRONIDAZOLE VERSUS METHYLPREDNISOLONE IN ACTIVE CROHN’S DISEASE
Medications
Corticosteroids
STEROID PREPARATIONS
SYSTEMIC CORTICOIDS
TOPICAL CORTICOIDS
RESULTS OF CORTICOSTEROID THERAPY
FOR CROHN’S DISEASE
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
Budesonide Pharmacology
• High topical potency
• High intrinsic activity
• Moderately high water solubility
• Affinity for glucocorticoid receptor – 200x hydrocortisone– 15x prednisolone
Hypothalamic-Pituitary Adrenal Axis
Oral Budesonide In Active Crohn’s Disease
Oral Budesonide As Maintenance Therapy For
Crohn’s Disease
Issues
• Post-surgery prevention• Steroid switching• Effect in children - growth etc• Side effects - bone• Quality of life• Activity in UC
Medications
Immunomodulators
AZATHIOPRINE AND 6-MERCAPTOPURINE
6-mercaptopurine in Active Crohn’s Disease
6-mercaptopurine and Azathioprine as
Maintenance Therapy in Crohn’s Disease
6-mercaptopurine as Maintenance Therapy for
Ulcerative Colitis
ADVERSE EFFECTS OF 6-MP/AZATHIOPRINE
Methotrexate for Active Crohn’s Disease
Methotrexate as Maintenance Therapy for
Crohn’s Disease
Medications
Cyclosporine-A
Cyclosporine in Active UC
TOXICITY OF CYCLOSPORINE
Medications
Biologicals Including Anti-TNF
ANTIBODIES TO TNF
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.
INFLIXIMAB IN ACTIVE CROHN’S DISEASE
INFLIXIMAB AS MAINTENANCE THERAPY FOR CROHN’S DISEASE
INFLIXIMAB FOR FISTULIZING CROHN’S
DISEASE
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
Rutgeerts et al. N Engl J Med, 2005
Anti-TNF for Maintenance in UC
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
Infliximab as Rescue TherapyResults
Janerot et al. Gastroenterology 2005
ADVERSE EFFECTS OF INFLIXIMAB
Medications
Emerging Treatments
EMERGING TREATMENTS FOR IBD-2002
TESTED UNCONVENTIONAL THERAPIES
GUIDELINES FOR PREGNANCY
NUTRITIONAL THERAPY IN IBD
INDICATIONS FOR SURGERY IN ULCERATIVE COLITIS
SURGICAL OPTIONS IN ULCERATIVE COLITIS
ILEAL POUCH-ANAL ANASTOMOSIS
LONG-TERM ADVERSE OUTCOMES OF ILEAL POUCH
ANAL ANASTOMOSIS
POUCHITIS
TREATMENT OPTIONS FOR POUCHITIS
INDICATIONS FOR SURGERY IN CROHN’S DISEASE
SURGICAL OPTIONS FOR INTRA-ABDOMINAL DISEASE
IN CROHN’S DISEASE
STRICTUROPLASTY (HEINEKE-MIKULICZ)
POST-OPERATIVE RECURRENCE RATES IN
CROHN’S DISEASE
CROHN’S DISEASE POST-OPERATIVE PROPHYLAXIS
MEDICAL TREATMENT OPTIONS FOR PERINEAL
DISEASE
SURGICAL TREATMENT OPTIONS FOR PERINEAL
CROHN’S DISEASE
THE DEAD SEA AND CROHN’S DISEASE –
Treatment of Fistuli