Transcript oral versus rectal mesalamine versus combination therapy in active

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