TNF-α Antagonists: Established Treatment for Crohn's Disease
The correct answer is (c) Crohn's disease—TNF-α antagonists are FDA-approved and guideline-recommended as first-line therapy for moderate to severe Crohn's disease, with proven efficacy in inducing remission, maintaining disease control, and closing fistulas. 1, 2
Why Crohn's Disease is the Correct Answer
FDA-Approved Indications
TNF-α antagonists (infliximab, adalimumab, golimumab) are FDA-approved specifically for:
- Reducing signs and symptoms and inducing/maintaining clinical remission in adult patients with moderately to severely active Crohn's disease who have inadequate response to conventional therapy 2
- Reducing draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing disease 2
- Pediatric Crohn's disease for reducing signs/symptoms and inducing/maintaining clinical remission 2
Guideline-Based Recommendations
The American Gastroenterological Association (AGA) identifies TNF-α antagonists as:
- Primary drug class for managing moderate to severe Crohn's disease (CDAI score ≥220) 1
- First-line therapy for fistulizing and cutaneous manifestations, particularly infliximab 1, 3
- Early introduction recommended—the AGA advises against delaying biologic therapy in moderate-to-severe disease 1, 3
Clinical Efficacy Evidence
Meta-analysis of 14 luminal Crohn's disease trials (3,995 patients) demonstrates:
- Induction of remission at week 4: 11% mean difference vs placebo (95% CI 6%-16%, P<0.001) 4
- Maintenance of remission at weeks 20-30: 23% mean difference in responders (95% CI 18%-28%, P<0.001) 4
- Fistula closure: 16% mean difference in maintenance trials (95% CI 8%-25%, P<0.001) 4
Important Caveat
Not all TNF antagonists are equally effective—etanercept does NOT induce remission of inflammatory bowel disease, unlike infliximab, adalimumab, and golimumab 1
Why the Other Options Are Incorrect
(a) Disseminated Intravascular Coagulopathy (DIC)
TNF-α antagonists have no established role in treating DIC. This is a coagulopathy requiring supportive care, treatment of underlying cause, and blood product replacement—not immunosuppressive biologics.
(b) Septic Shock
TNF-α antagonists are contraindicated in active serious infections 2. Despite theoretical rationale for blocking inflammatory cytokines in sepsis, clinical trials have not demonstrated benefit, and these agents increase infection risk, making them inappropriate for septic shock management.
(d) Metastatic Melanoma
TNF-α antagonists increase malignancy risk rather than treat it 2. The FDA black box warning specifically notes lymphoma and other malignancies in patients treated with TNF blockers 2. Metastatic melanoma requires immunotherapy (checkpoint inhibitors), targeted therapy, or chemotherapy—not TNF antagonism.
Clinical Dosing for Crohn's Disease
Standard infliximab regimen: 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks 2
- Some patients who initially respond but later lose response may benefit from dose escalation to 10 mg/kg 2