IBD IBD Pharmacotherapy 2 — Questions and Answers
Question 1: Ustekinumab (Stelara) targets which cytokine pathway in treating Crohn's disease?
- TNF-α and lymphotoxin
- IL-12 and IL-23 via the p40 subunit (Correct answer)
- IL-4 and IL-13
- IFN-γ directly
Correct answer: IL-12 and IL-23 via the p40 subunit
Ustekinumab is a fully human monoclonal antibody targeting the shared p40 subunit of IL-12 and IL-23, blocking Th1 and Th17 immune responses.
Question 2: Which serious opportunistic infection risk requires tuberculosis (TB) screening before initiating anti-TNF therapy in IBD?
- TNF blockade impairs macrophage killing of Mycobacterium tuberculosis, risking TB reactivation (Correct answer)
- Anti-TNF drugs directly activate latent TB virus
- TNF inhibitors increase gut permeability to mycobacteria
- Anti-TNF therapy depletes NK cells selectively
Correct answer: TNF blockade impairs macrophage killing of Mycobacterium tuberculosis, risking TB reactivation
TNF-α is critical for granuloma maintenance and mycobacterial containment; blocking it can reactivate latent TB, requiring screening (PPD/IGRA) before treatment.
Question 3: Tofacitinib (Xeljanz) is approved for which IBD indication in the United States?
- Moderately to severely active Crohn's disease
- Moderately to severely active ulcerative colitis (Correct answer)
- Pouchitis after IPAA surgery
- Mild ulcerative colitis as first-line therapy
Correct answer: Moderately to severely active ulcerative colitis
Tofacitinib, a JAK1/JAK3 inhibitor, is FDA-approved for moderately to severely active UC in adults who have failed TNF inhibitors.
Question 4: Metronidazole and ciprofloxacin in Crohn's disease are most appropriate for treating which complication?
- Luminal small bowel disease
- Perianal fistulas and abscesses (Correct answer)
- Crohn's-related arthropathy
- Small bowel strictures
Correct answer: Perianal fistulas and abscesses
Antibiotics like metronidazole and ciprofloxacin are used adjunctively for perianal fistulas and abscesses in Crohn's disease, targeting polymicrobial perianal flora.
Question 5: Combination therapy with infliximab and azathioprine is superior to monotherapy primarily because of which pharmacological interaction?
- Azathioprine enhances TNF-α production
- Azathioprine reduces infliximab immunogenicity by suppressing anti-drug antibody formation (Correct answer)
- Azathioprine increases infliximab receptor binding
- They have synergistic effects on JAK-STAT signaling
Correct answer: Azathioprine reduces infliximab immunogenicity by suppressing anti-drug antibody formation
Azathioprine reduces the formation of anti-infliximab antibodies (immunogenicity), maintaining higher trough levels and prolonging infliximab efficacy.
Question 6: Which IBD medication carries a Black Box Warning for increased risk of lymphoma, specifically hepatosplenic T-cell lymphoma?
- Vedolizumab
- Mesalamine
- Thiopurines (azathioprine/6-MP) especially in young males (Correct answer)
- Ustekinumab
Correct answer: Thiopurines (azathioprine/6-MP) especially in young males
Thiopurines, particularly in young males under 35, carry a risk of hepatosplenic T-cell lymphoma (HSTCL), a rare but often fatal lymphoma.
IBD IBD Pharmacotherapy 2
Ustekinumab (Stelara) targets which cytokine pathway in treating Crohn's disease?