immunomodulators and biologic therapy for inflammatory

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INFLAMMATORY BOWEL
DISEASE
IMMUNOMODULATORS AND
BIOLOGIC THERAPY
Inflammatory Bowel Disease
(IBD)

IBD
◦ Subgroups or types of IBD:
 Crohns Disease (CD)
 Ulcerative Colitis (UC)
◦ Onset across all ages reported in as young as
preschoolers
◦ More commonly onset in adolescent age
IBD: MULTI-FACTORIAL
ETIOLOGY
Environmental Trigger
IBD
Genetic Predisposition
Immune Response
Manifestations of IBD:
Crohn’s Disease (CD)
◦ Extends throughout the GI tract: from mouth to anus;
◦ Commonly affects the terminal ileum & colon (terminal
ileitis)
◦ Involves all layers of bowel wall (transmural)
◦ Pain characteristic to RLQ
◦ Fistula/fissure/stricture development
◦ Extra-intestinal symptoms, uveitis, large joint / arthritis,
mouth ulcers, liver disease, renal calculi, cutaneous
manifestations (erythema nodosum)
◦ May require surgery to manage complications
◦ Medical management, life long condition
Manifestations of IBD:
Ulcerative Colitis (UC)
◦
◦
◦
◦
Limited to colon & rectum
Involves the mucosa & submucosal layer
Pain characteristic to LLQ
Extraintestinal symptoms as with Crohn’s
except for apthous lesions
◦ Medical management
◦ Curative surgery is a colectomy
IBD: Signs and Symptoms
Abdominal pain / cramps
 Fatigue
 Anorexia, weight loss and decreased growth velocity
 Nocturnal symptoms
 Systemic symptoms may be present for months or years
prior to GI symptoms and diagnosis (CD)
 Diarrhea (bloody more common with UC)
 Extraintestinal involvement: joint and muscle pains, apthous
oral ulcers (CD), uevitis
 Periods of exacerbations and remissions
 Sometimes differentiation between CD and UC may be
difficult to determine. When differentiation is not obvious
the IBD may be classified as “Indeterminate Colitis”

Diagnostic Workup

Abdominal series to evaluate structure and anatomy

Labs: CBC, Inflammatory markers (ESR and CRP)

Stool studies to rule out infectious origin

Endoscopy (upper & lower may be indicated for CD) with
biopsy and histiologic evaluation

Serum antibody markers help to confirm diagnosis
(perinuclear antineutrophil cytoplasmic antibodies [PANCA] and anti-Saccharomyces cerevisiae antibodies
[ASCA]); Testing + for P–ANCA more likely to have UC
while children who test + for ASCA are more likely to have
Crohn’s)
Nutrition as Treatment

Low residue diet

Nutrition is a significant first line therapy for CD
◦ (nutrition delivered by mouth, NG/G-tube or parenteral
nutrition)

Nutrition is a supplemental therapy for UC

Vitamin and mineral supplementation
(vitamin B12, folic acid, calcium, Vitamin D, iron)
Pharmaceutical Treatment

Aminosalicylics – anti-inflammatory; induces remission,
administered topically PR

Antibiotics-reduce bacterial burden in the gut

Steroids-induces remission and control inflammation for
maintenance therapy

Immunomodulators- suppress activated inflammation;
maintenance and remission

Biologics-antibodies act on specific molecules in the
immune cascade; maintenance and remission
IBD Pharmacologic
Therapies
BIOLOGICS (moderate-severe disease)
IMMUNMODULATORS (moderate-severe disease)
ANTIBIOTICS (mild to moderate disease)
STEROIDS (moderate to severe disease)
AMINOSALICYLATES (mild to moderate disease)
1st three levels are mainstay of a traditional step up approach
for pharmacological therapy. A combination of these agnets
may be administered. This approach starts with the least
toxic medical regime and advances in therapy are
determined based on response. Immunomodulators and
biologics are added when there has been a lack of response
or side effects/ toxicities are manifested.
Indications for Immunomodulators
and/or Biologics

Unresponsive to aminosalicyclates, steroids and
antibiotics

Steroid refractory/ steroid dependence

Perianal disease not responding to antibiotics

Fistula / stricture formation

Maintenance of remission

May combine therapies with lower dose steroids
to achieve a “steroid sparing” effect
References
Crohn’s and Colitis Foundation of America. www.ccfa.org
Lichtenstein, G.R., Abreu, M.T., Cohen, R., and Tremaine, W. (2006). American
Gastroenterological Association Institute: American gastroenterological
association institute medical position statement on corticosteroids,
immunomodulators, and infliximab in inflammatory bowel disease.
Gastroenterology 130 935-939.
MacDermott, R.P, (2008) 6-mercaptopurine (6-MP) metabolite monitoring and
TMPT testing in the treatment of inflammatory bowel disease with 6-MP or
azathioprine. UpToDate retrieved 1/14/09 www.uptodate.com
Prometheus® 2008. Prometheus thiopurine management.
Prometheus laboratories. San Diego CA www.prometheuslabs.com
Sanborn, W.J. (1996). A review or immunomodifier therapy for inflammatory
bowel disease: Azathioprine, 6-mercaptoputine, cyclosporine, and
methotrexate
REFERENCES
Snapper, S.B. and Podolsky, D.K. (2008 Immune and microbial mechanisms in the
pathogenesis of inflammatory bowel disease. UptoDate retrieved 1/14/09
www.uptodate.com
Su, C. & Lichtensteien, G.R. (2004). Treatment of inflammatory bowel disease with
azathioprine and 6-mercaptopurine. Gastroenterology Clinics of North America
33 209-234.
Taketomo, C.K. Hodding, J.H. and Kraus, Donna, M. (2008-2009). Pediatric dosage
handbook. 15th edition LEXI-COMP
Van Deventer, S.J. (1999). Anti-TNF antibody treatment of Crohn’s disease. Annals
of Rheumatic Diseases 58 S-, 1140-1120
Wyneski, M.J., Green, A., Kay, M., Wyllie, R., Mahajan, L. (2008).
Safety and efficacy of adalimumab in pediatric patients with Crohn disease.
Journal of Pediatric Gastroenterology and Nutrition47(1) 19-25
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