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Inflammatory Bowel Disease Treatment Response to treatment Pathology Imaging Laboratory Clinical Epidemiology 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 6MERCAPTOPURINE 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 6MP/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. Cytokine Monoclonal antibody Cytokine receptor No signal Choy EHS et al. N Engl J Med. 2001;344:907–16. 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 1 - 46w ACT 2 - 30w Rutgeerts et al. N Engl J Med 2005 Anti-TNF for Maintenance in UC Rutgeerts et al. N Engl J Med, 2005 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 POSTOPERATIVE 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
