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 DiseaseMaintenance
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
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 weeks ACT w ACT w 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 Therapy Results 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