A 32-year-old woman from Delhi presents with a 6-month history of bloody diarrhoea, abdominal cramping, and tenesmus. Colonoscopy reveals continuous mucosal inflammation limited to the colon with crypt abscesses on biopsy. She is started on induction therapy. After 4 weeks of standard therapy, her symptoms persist with 6–8 stools daily and faecal calprotectin of 380 μg/g. Which of the following is the most appropriate next step in management?

Explanation

## Clinical Scenario Analysis This patient has **ulcerative colitis** (UC) with: - Continuous colonic inflammation (diagnostic of UC) - Inadequate response to standard induction therapy (mesalamine + corticosteroids implied) - Persistent high faecal calprotectin indicating active inflammation ## Treatment Escalation in UC **Key Point:** Patients with moderate-to-severe UC who fail to respond to standard induction therapy (5-ASA agents ± corticosteroids) within 4 weeks require escalation to immunosuppressive or biologic therapy. ### Why Infliximab is Correct **High-Yield:** TNF-α inhibitors (infliximab, adalimumab) are the gold standard for: 1. **Steroid-refractory UC** — failure to respond to adequate corticosteroid therapy 2. **Steroid-dependent UC** — relapse on tapering or inability to taper below 7.5 mg prednisolone daily 3. **Moderate-to-severe active disease** unresponsive to 5-ASA agents **Clinical Pearl:** Infliximab is administered as an induction regimen: - Doses at weeks 0, 2, and 6 - Maintenance dosing every 8 weeks thereafter - Efficacy demonstrated in multiple RCTs (ACT trials) for UC ### Mechanism of Action Infliximab is a **chimeric monoclonal antibody** against TNF-α: - Binds soluble and membrane-bound TNF-α - Reduces pro-inflammatory cytokine cascade - Induces apoptosis of activated T cells - Restores intestinal barrier function ## Treatment Algorithm for UC Induction Failure ```mermaid flowchart TD A[Mild-moderate UC]:::outcome --> B[5-ASA + topical corticosteroids] C[Moderate-severe UC]:::outcome --> D[5-ASA + systemic corticosteroids] D --> E{Response at 4 weeks?}:::decision E -->|Yes| F[Taper corticosteroids]:::action E -->|No| G[Escalate therapy]:::action G --> H{Steroid-refractory or dependent?}:::decision H -->|Yes| I[TNF-α inhibitor<br/>infliximab/adalimumab]:::action H -->|No| J[Add azathioprine<br/>or 6-mercaptopurine]:::action I --> K[Induction: weeks 0, 2, 6]:::action K --> L[Maintenance: every 8 weeks]:::action ``` ## Why Other Options Are Suboptimal | Option | Rationale for Rejection | |--------|------------------------| | **Increase mesalamine to 4.8 g/day** | Already failed standard therapy; dose escalation alone insufficient for steroid-refractory disease. 5-ASA agents are ineffective monotherapy for moderate-severe UC. | | **Add azathioprine 2 mg/kg/day** | Appropriate for **steroid-dependent** disease, not steroid-refractory. Onset is slow (8–12 weeks); patient needs rapid control. | | **Oral budesonide 9 mg/day** | Budesonide is a **colonic-release formulation** used for mild-moderate UC; ineffective for moderate-severe disease and does not induce remission in steroid-refractory cases. | **Warning:** Do not confuse budesonide (topical corticosteroid for distal colitis) with systemic corticosteroids. This patient has already failed corticosteroid induction and requires biologic therapy. ## Pre-Treatment Screening for Infliximab **Key Point:** Before initiating TNF-α inhibitors, mandatory screening includes: - Tuberculosis (TST or IGRA) - Hepatitis B and C serology - Complete blood count and liver function tests - HIV serology (in high-risk populations) [cite:Harrison 21e Ch 295]