Biologic therapies for IBD

Biologics Overview - Targeted Takedown

• Monoclonal antibodies engineered to neutralize specific inflammatory mediators.
• Major classes for IBD:
  • Anti-TNF (e.g., Infliximab)
  • Anti-Integrin (e.g., Vedolizumab)
  • Anti-IL-12/23 (e.g., Ustekinumab)
• Used for moderate-to-severe disease, often after conventional therapy fails. Requires pre-screening for infections.

⭐ Screen for latent TB before starting anti-TNF agents due to high risk of reactivation.

Anti-TNF-α Agents - The TNF Blockade

• Mechanism: Monoclonal antibodies that bind and neutralize TNF-α, preventing it from binding to its receptors and triggering pro-inflammatory signaling.
• Agents:
  • Infliximab (chimeric)
  • Adalimumab (human)
  • Certolizumab pegol (humanized Fab' fragment; approved for Crohn's)
  • Golimumab (human; approved for UC)
• Indications: Moderate-to-severe IBD (both UC and Crohn's) refractory to conventional therapy; fistulizing Crohn's disease.
• Key Adverse Effects:
  • ↑ Infection risk (esp. reactivation of latent TB)
  • Infusion/injection site reactions
  • Demyelinating diseases
  • Worsening heart failure

⭐ High-Yield: Always screen for latent TB (PPD or IGRA) and Hepatitis B virus before initiating anti-TNF-α therapy due to risk of reactivation.

Anti-Integrins - Gut-Specific Gatekeepers

• Mechanism: Selectively block gut-homing lymphocytes.
  • Vedolizumab binds to the α4β7 integrin on T-cells.
  • Prevents their interaction with MAdCAM-1 on gut endothelial cells.
  • This inhibits lymphocyte trafficking into the GI tract lamina propria.
• Use: Moderate-to-severe Ulcerative Colitis & Crohn's Disease, especially after anti-TNF failure.
• Key Advantage: Gut-selective action minimizes systemic immunosuppression.

⭐ High-Yield: Unlike Natalizumab (α4β1/α4β7), Vedolizumab's gut-specificity (α4β7) spares CNS immune surveillance, virtually eliminating the risk of Progressive Multifocal Leukoencephalopathy (PML).

Anti-IL-12/23 Agents - Cytokine Control

• Ustekinumab: Human monoclonal antibody targeting the p40 subunit shared by Interleukin-12 (IL-12) and Interleukin-23 (IL-23).
• Mechanism:
  • Blocks IL-12 → ↓ Th1 cell differentiation.
  • Blocks IL-23 → ↓ Th17 cell pathway activation.
• Use: Moderate-to-severe Crohn's & Ulcerative Colitis, especially after anti-TNF failure.
• Risks: ↑ Infection risk (TB screening required), nasopharyngitis; rare reversible posterior leukoencephalopathy syndrome (RPLS).

⭐ By targeting the common p40 subunit, ustekinumab uniquely disrupts both the Th1 and Th17 inflammatory axes.

Pre-Biologic Screening - Safety First Protocol

• Core Principle: Identify and treat latent infections to prevent reactivation, especially with TNF-α inhibitors.
• Tuberculosis (TB) Screening: Mandatory.
  • Interferon-Gamma Release Assay (IGRA) or Tuberculin Skin Test (PPD).
  • Positive screen requires a chest X-ray to exclude active TB.
• Viral Hepatitis & HIV Screening:
  • Hepatitis B panel: HBsAg, anti-HBs, anti-HBc.
  • Hepatitis C antibody.
  • HIV test.
• Vaccination Update:
  • Ensure all vaccinations are current.
  • ⚠️ Administer live vaccines ≥4 weeks BEFORE biologic initiation.

⭐ TNF-α inhibitors carry a high risk of reactivating latent TB. If screening is positive, treatment for latent TB (e.g., Isoniazid) must be initiated before starting the biologic.

High-Yield Points - ⚡ Biggest Takeaways

• Anti-TNF agents (e.g., infliximab) require screening for latent TB before initiation due to reactivation risk.
• They can also exacerbate congestive heart failure and increase risk for invasive fungal infections.
• Vedolizumab is a gut-specific anti-integrin (α4β7) with fewer systemic immunosuppressive effects than anti-TNF agents.
• Natalizumab carries a high risk of Progressive Multifocal Leukoencephalopathy (PML), limiting its use.
• Ustekinumab targets IL-12 and IL-23 and is effective for both Crohn's and ulcerative colitis.