A 35-year-old woman with a 3-year history of Crohn's disease (involving terminal ileum and colon) presents with recurrent flares despite adequate mesalamine therapy. She has had two hospitalizations in the past year and is now experiencing abdominal pain, diarrhea, and weight loss. Colonoscopy shows patchy, transmural inflammation with skip lesions. She has no active infections. What is the drug of choice for inducing remission in this patient?

## Induction Therapy in Moderate-to-Severe Crohn's Disease **Key Point:** TNF-α inhibitors (infliximab, adalimumab) are the gold-standard induction agents for moderate-to-severe Crohn's disease, especially when conventional therapy (corticosteroids, 5-ASA) has failed or is inadequate. ### Why Infliximab in This Case 1. **Inadequate response to 5-ASA:** Mesalamine is ineffective in Crohn's disease (unlike UC) 2. **Moderate-to-severe disease:** Multiple flares, hospitalization, weight loss, transmural inflammation 3. **No contraindications:** No active infection, immunosuppression is appropriate ### Mechanism of Action - Chimeric monoclonal antibody against TNF-α - Blocks TNF-α-mediated inflammation and T-cell activation - Induces apoptosis of activated lymphocytes ### Dosing Regimen (REMICADE) - **Induction:** 5 mg/kg IV at weeks 0, 2, and 6 - **Maintenance:** 5 mg/kg IV every 8 weeks (after induction) - **Response rate:** 60% clinical response, 30–40% remission at 4 weeks ### Comparison of TNF-α Inhibitors in Crohn's Disease | Agent | Route | Induction Dose | Maintenance | Onset | |---|---|---|---|---| | **Infliximab** | IV | 5 mg/kg at 0, 2, 6 weeks | 5 mg/kg q8 weeks | 2 weeks | | **Adalimumab** | SC | 160 mg (or 80 mg if <40 kg) at week 0 | 40 mg q2 weeks | 2–4 weeks | | **Certolizumab pegol** | SC | 400 mg at 0, 2, 4 weeks | 400 mg q4 weeks | 2–4 weeks | **High-Yield:** Infliximab is the most rapidly acting TNF-α inhibitor and is preferred for acute, severe flares. Adalimumab is an alternative for patients who prefer subcutaneous dosing. ### Pre-Treatment Screening - TB screening (TST, IGRA) — mandatory - Hepatitis B and C serology - CBC, LFTs - Pregnancy test (if applicable) **Clinical Pearl:** Combination therapy with azathioprine or 6-mercaptopurine reduces immunogenicity (anti-TNF antibody formation) and improves long-term efficacy of TNF-α inhibitors. ### Monitoring During Induction - Clinical response at 2 weeks (abdominal pain, stool frequency) - Assess for adverse effects (infusion reactions, infections) - CRP/ESR at 4 weeks **Warning:** Do NOT use TNF-α inhibitors in active tuberculosis or untreated latent TB. Risk of disseminated TB is significantly increased. [cite:Harrison 21e Ch 297]