TNF-α Antagonists: Established Efficacy in Crohn's Disease
The correct answer is (c) Crohn's disease—TNF-α antagonists are FDA-approved and guideline-recommended as highly effective therapy for moderate to severe luminal and fistulizing Crohn's disease, with proven benefits in inducing and maintaining clinical remission. 1
Approved Indications for TNF-α Antagonists in Crohn's Disease
TNF-α antagonists (infliximab, adalimumab, certolizumab pegol, golimumab) are specifically approved 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 1
- Reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing disease 1
- Pediatric Crohn's disease for reducing signs and symptoms and inducing/maintaining clinical remission 1
Evidence Supporting Use in Crohn's Disease
The American Gastroenterological Association (AGA) guidelines identify TNF-α antagonists as a primary drug class for managing moderate to severe Crohn's disease (CDAI score ≥220) 2. Over the past 20 years, these agents have been approved for multiple inflammatory diseases, with particularly strong efficacy demonstrated in Crohn's disease 2.
For luminal disease: Meta-analysis demonstrates TNF antagonists are effective for induction of remission at week 4 (mean difference 11%; 95% CI, 6%-16%; P<0.001) and maintenance of remission at weeks 20-30 (mean difference 23%; 95% CI, 18%-28%; P<0.001) 3.
For fistulizing disease: Infliximab, adalimumab, and golimumab can induce clinical and endoscopic remission of inflammatory bowel disease, with proven efficacy in fistula closure 2. The AGA specifically recommends anti-TNF-α biologics, particularly infliximab, as first-line therapy for patients with fistulizing and cutaneous manifestations 4.
Why the Other Options Are Incorrect
(a) Disseminated intravascular coagulopathy (DIC): TNF-α antagonists have no established role in treating DIC. This is a hematologic emergency requiring treatment of the underlying cause, supportive care, and potentially blood product replacement.
(b) Septic shock: TNF-α antagonists are contraindicated in active serious infections 1. While TNF-α plays a role in sepsis pathophysiology, clinical trials of TNF antagonists in septic shock have not demonstrated benefit and may cause harm by impairing host defense mechanisms.
(d) Metastatic melanoma: TNF-α antagonists are not used to treat melanoma. In fact, the FDA black box warning specifically notes that lymphoma and other malignancies, some fatal, have been reported in patients treated with TNF blockers 1. These agents suppress immune surveillance and would be contraindicated in active malignancy.
Important Safety Considerations
When prescribing TNF-α antagonists for Crohn's disease, clinicians must:
- Screen for latent tuberculosis before initiating therapy and monitor for active TB during treatment 1
- Discontinue therapy if serious infection develops 1
- Be aware of increased malignancy risk, particularly hepatosplenic T-cell lymphoma in young males receiving concomitant azathioprine or 6-mercaptopurine 1
- Avoid doses >5 mg/kg in moderate to severe heart failure 1
Clinical Pearls
- Primary nonresponse occurs in up to one-third of patients, and 23-50% experience loss of response during treatment 5
- The AGA advises against delaying biologic therapy in patients with moderate-to-severe disease and recommends early introduction of biologics with or without immunomodulators 4
- Not all TNF antagonists are equally effective for fistulizing disease—etanercept does not induce remission of inflammatory bowel disease, unlike infliximab, adalimumab, and golimumab 2
- Therapeutic drug monitoring plays an important role when patients show inadequate response 5