IBD Pharmacology Part 2: Biologics and Small Molecules
Anti-TNF biologics · JAK inhibitors · Gut-selective biologics · Therapeutic drug monitoring
Anti-Tumor Necrosis Factor Biologics
Agent Structure Route Key Advantage Key Consideration
Infliximab Chimeric IgG1 (25% murine) IV infusion Most clinical trial data; biosimilars available More immunogenic; anti-drug antibody risk higher
Adalimumab Fully human IgG1 SC every 2 weeks Self-injection; lower immunogenicity than infliximab Anti-drug antibodies still form; biosimilars available
Certolizumab PEGylated Fab’ (no Fc) SC monthly No placental transfer — preferred in pregnancy Approved for CD only (not UC) in most markets
Golimumab Fully human IgG1 SC monthly Monthly maintenance dosing Approved for UC only
Gut-Selective and IL-23 Biologics
Vedolizumab
Alpha-4-Beta-7 Integrin Blocker
  • Blocks gut-homing lymphocyte trafficking to intestinal mucosa
  • Gut-selective: systemic immunity preserved
  • No TB screening required; no increased systemic infection risk
  • Preferred in elderly and high-infection-risk patients
  • Slower onset in CD (response by week 10–14)
  • Approved: UC and CD
Ustekinumab
Anti-IL-12/23 p40
  • Blocks p40 subunit shared by IL-12 and IL-23
  • Suppresses both Th1 (IL-12) and Th17 (IL-23) pathways
  • IV induction then SC maintenance every 8–12 weeks
  • Excellent safety profile; no TB reactivation risk
  • Effective for extraintestinal manifestations
  • Approved: UC and CD
Risankizumab
Selective Anti-IL-23 p19
  • Blocks IL-23 p19 only — spares IL-12
  • Preserves IL-12-dependent antiviral and antimycobacterial immunity
  • IV induction (weeks 0, 4, 8) then SC every 8 weeks
  • Favorable infection and malignancy profile
  • Approved: UC and CD
JAK Inhibitors
Advantages Over Biologics
Oral, Rapid, Non-Immunogenic
  • Oral bioavailability — no injection or infusion
  • Rapid onset: response within days
  • No immunogenicity — no anti-drug antibodies
  • Tofacitinib: JAK1/3 selective; UC only
  • Upadacitinib: JAK1 selective; UC and CD
2022 FDA Black Box Warning
MACE, VTE, Malignancy
  • Use only after inadequate response to TNF inhibitor
  • Increased MACE, venous thromboembolism, malignancy vs. TNF inhibitors
  • Avoid in age ≥50 with cardiovascular risk factors
  • Herpes zoster risk increased: vaccinate before starting
  • Monitor lipids (LDL elevation occurs)
Loss of Response: Use TDM to Guide Next Step
Mechanism Trough Level Anti-Drug Antibodies Management
Pharmacokinetic failure Low Low or absent Dose-escalate or shorten interval
Immunogenic failure Low High Switch anti-TNF agent or switch biologic class
Pharmacodynamic failure Adequate Low or absent Switch biologic class — do not dose-escalate
Primary non-response Any Any Switch biologic class immediately
Pre-Biologic Screening — All Anti-TNF Agents

TB screening (TST or IGRA + chest X-ray) and hepatitis B serology before every anti-TNF start. Treat latent TB at least 4 weeks before starting. Update all vaccines; no live vaccines once biologic is active.