Approaches to IBD treatment

• Minimize symptoms

• Slow down progression

• Improve QOL

• Relieve inflammatory process

• induce and maintain remission

• Surgery

• Normal bowel frequency

Goals of treatment

Nutritional support and Surgery

Two Non-Pharm options for IBD

• Malabsorption or maldigestion secondary to catabolic effects of disease

• Increased IL-6 and TNF-α 🡪 increase protein turnover 🡪 protein loss and muscle wasting

• Crohn’s disease patients at higher risk for malnutrition due to small bowel involvement

Nutritional support in IBD points - Causes of malnutrition

• Eliminate foods that exacerbate symptoms 🡪 red meats, sulfur, and alcoholic beverages; lactose for lactase deficiency

• Avoid citrus fruits and nuts in those with small bowel strictures to prevent obstruction

• Increase soluble fiber for potential anti-inflammatory effects

• Enteral nutrition

  • Increase in nutritional status and decrease in inflammation

  • Promote mucosal healing

• Parenteral nutrition has limited role

Probiotics - Less compelling evidence

Nutritional support in IBD points - Management = Probiotics

• Rates of colectomy in 20 years = 0.5-20%

• Necessary when disease uncontrolled by maximum medical therapy or complications (toxic megacolon, perforation, hemorrhage)

• Prophylactic measure for those with long-standing disease and at risk for colorectal carcinoma

• Restorative proctocolectomy with ileal pouch anal anastomosis is most common procedure

• CURATIVE!!!

Surgery options as non-pharm for IBD - UC

• Rates of surgical intervention in 10 years = 40-55%

  • 5-year postop recurrence rate = 50%

• Reserved for patients with intractable hemorrhage, perforation, persistent obstruction, or refractory disease

• Resection of major intestinal areas of involvement

  • Multiple resections can lead to short gut syndrome

• NON-CURATIVE

Surgery options as non-pharm for IBD - CD

1. Aminosalicylates

2. Corticosteroids

3. Immunomodulators

4. Biologics

5. Small molecule inhibitors

6. Immunosuppressants

The 6 classes of pharmacologic therapies in IBD!!!

• Used mostly for UC > CD

• Sulfasalazine is prodrug for mesalamine

• Mesalamine acts in GI tract 

• MOA UNCLEAR - maybe scavenge free radicals, inhibit motility of leukocytes, interfere with TNF-α, inhibit leukotriene and prostaglandin

Aminosalicylates points

• Sulfasalazine (prodrug)

• Mesalamine (SUPP, enema, and oral)

• Balsalazide

The Specific Aminosalicylate drugs

• Headache

• Nausea

• Diarrhea

• Interstitial nephritis

• Sulfasalazine only: hemolytic anemia, leukopenia, hepatitis  sulfa allergy
  

Aminosalicylates Adverse effects

Budesonide

• Oral, controlled release preparation or rectal foam

• Releases in the terminal ileum (oral) or colon (rectal foam)

• Minimal systemic exposure due to first-pass metabolism

Prednisone/Methylprednisolone

• For acute treatment of flares to suppress inflammatory response

• Not for long-term use as maintenance therapy

Corticosteroids points

• budesonide

• prednisone

• Hydrocortisone

• Methlyprednisolone

The specific Corticosteroids used in IBD

For prednisone/methylprednisolone:

Hyperglycemia, psychosis, hypertension, osteoporosis, weight

Corticosteroids AE’s

Azathioprine & Mercaptopurine

• Used for long-term treatment of Crohn’s disease and ulcerative colitis

• Reserved for patients who have failed ASA therapy or refractory to or dependent on systemic corticosteroids

• Can be used in conjunction with mesalamine, biologics, or corticosteroids 

• Must be used for extended periods of time (weeks to months) to see beneficial outcomes

Methotrexate

• May be useful for maintenance therapy of Crohn’s disease for steroid-sparing effects

• Data for use in ulcerative colitis was no better than placebo

Immunomodulators points

• Azathioprine

• Mercaptopurine

• Methotrexate 

The specific immune modulator drugs used in IBD

• Bone marrow suppression, hepatotoxicity, rash, arthralgias 

• *Must test for TPMT before initiation

Immune Modulators AE’s

• Infliximab

• Adalimumab

• Certolizumab

• Golimumab

Binds to TNF-α inhibiting pro-inflammatory activity

The TNF-a inhibitors used in IBD (mabs) - IACG

• *Must test for HBsAg and T-SPOT/PPD

• Infusion or injection site reactions

• Reactivation of hepatitis B virus

• Reactivation of tuberculosis

• Lymphoma

• Anti-drug antibodies

TNF-a inhibitors AE’s

• Ustekinumab (IL-23 & IL-12)

• Risankizumab (IL-23 via p19)

• Mirikizumab (IL-23 via p19)

• Guselkumab (IL-23 via CD64)
  

Binds to IL-23 inhibiting pro-inflammatory activity

IL-23 Antagonists used in IBD specifically

• Infusion or injection site reactions

• Reactivation of hepatitis B virus

• Reactivation of tuberculosis

• Lymphoma

IL-23 Antagonists AE’s

Vedolizumab - inhibitor that inhibits leukocyte adhesion and migration by targeting α4β7 subunit of integrin

AE’s

• Infusion or injection site reactions

• Reactivation of hepatitis B virus

• Reactivation of tuberculosis

• Lymphoma

• Anti-drug antibodies

Anti-integrins used in IBD treatment + AE’s

• Tofacitinib (Xeljanz)

• Upadacitinib

prevent cytokine and intracellular activity of immune cells leading to a decrease inflammatory and immune response

JAK inhibitors used specifically in IBD treatment

• Acne

• Thrombosis

• Elevated liver enzymes

• Cardiovascular Events

JAK inhibitors AE’s

• Etrasimod

• Ozanimod

Bind to S1P_1,4,5 receptors resulting in partial, reversible blockade of lymphocyte outlet from lymphoid organs and decreased number of lymphocytes in the peripheral blood > reduction in lymphocyte migration to intestines

S1P receptor modulators specifically used in IBD

• Bradycardia

• Hypertension

• Orthostatic Hypotension

• Skin cancer

• Elevated liver enzymes

• Lymphocytopenia

• Macular Edema

• Varicella

• **requires baseline EKG, skin exam, eye exam, and CBC with differential

S1P receptors modulators AE’s