Inflammatory Bowel Disease Treatment Goals

Inflammatory Bowel Disease (IBD) Treatment Goals

• IBD treatment aims to:
  • Rest the bowel
  • Control inflammation
  • Correct malnutrition
  • Provide symptomatic relief
  • Improve quality of life
• No cure exists for IBD

Drug Therapy for IBD

• The goal is to induce and maintain remission
• Five main drug classes are used:
  • Aminosalicylates
  • Antimicrobials
  • Corticosteroids
  • Immunomodulators
  • Biologic therapies
• Drug choice depends on inflammation location and severity
• Initial ulcerative colitis (UC) treatment includes corticosteroids for symptom relief, then aminosalicylates or biologics based on severity
• Crohn's disease management also includes biologics and corticosteroids, possibly as combinations.

Aminosalicylates (5-ASA)

• Treat both UC and Crohn's, being more effective for UC
• Mechanism unclear, thought to suppress pro-inflammatory cytokines and mediators
• Administered orally or rectally
• Oral forms have different coatings affecting drug release, improving targeted symptom relief
• Rectal delivery is beneficial for inflammation in rectum/large intestine
• Combination therapy (oral and rectal) is better than oral or rectal alone.

Biologic Therapies

• Reduce IBD inflammation by blocking specific inflammatory proteins
• Four main classes:
  • Anti-TNF agents
  • Alpha 4-integrin inhibitors
  • IL-12/23 antagonists
  • JAK inhibitors
• Anti-TNF agents (e.g., infliximab) are given intravenously (IV) to induce/maintain remission in UC/Crohn's
• Other anti-TNF agents are subcutaneous (SQ)
• Common side effects (all anti-TNF agents): upper respiratory/urinary tract infections, headaches, nausea, joint/abdominal pain
• More serious side effects: hepatitis reactivation, TB, opportunistic infections, cancers (especially lymphoma)
• Testing for TB and hepatitis is required before starting anti-TNF therapy
• Active infections delay treatment
• Live virus immunizations are contraindicated
• Education on preventing/recognizing infection symptoms (fever, cough, malaise, dyspnea) is crucial

Alpha 4-Integrin Inhibitors

• (e.g., natalizumab, vedolizumab)
• Inhibit leukocyte adhesion by blocking α4-integrin
• Only used when other therapies (corticosteroids, immunomodulators, anti-TNFs) haven't been effective
• Administered by IV infusion
• Side effects include increased infection risk, liver toxicity, and hypersensitivity reactions
• Natalizumab is restricted for use.

IL-12/23 Antagonists

• (e.g., ustekinumab, risankizumab)
• Inhibit IL-12 and IL-23, preventing T-helper and natural killer cell activation
• Administered by IV first dose, then via injections every 8 weeks.
• Precautions and side effects similar to anti-TNF agents.

JAK Inhibitors

• (e.g., tofacitinib)
• Suppress the immune system by blocking the JAK enzyme.
• Prevent immune cell activation causing inflammation.
• TB testing required before starting
• Should not be combined with other biologics or immunomodulators

Corticosteroids

• Decrease intestinal mucosa inflammation
• Short-term use due to side effects of long-term use
• Suppositories, enemas, and foams deliver corticosteroids directly to inflamed tissue in the sigmoid, rectum, and left colon.
• Oral prednisone is for mild-to-moderate disease unresponsive to 5-ASA.