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