Medicine · Inflammatory Bowel Disease and GIT Disorders (IBD, Malabsorption, PUD)

A 28-year-old man with Crohn's disease (colonic and ileocolonic involvement, CDAI 320) has failed azathioprine therapy. He tests negative for TB and hepatitis B. Per current ACG and ECCO 2023 guidelines, what is the preferred step-up therapy?

  • A Infliximab (anti-TNF) alone
  • B Ustekinumab (anti-IL12/23) as preferred over anti-TNF in all Crohn's patients
  • C Vedolizumab (anti-integrin) for all Crohn's patients failing immunomodulators
  • D Infliximab plus azathioprine (combination therapy, SONIC trial evidence)
Correct answer: D. Infliximab plus azathioprine (combination therapy, SONIC trial evidence)

Explanation

The SONIC trial demonstrated that combination therapy with infliximab plus azathioprine is superior to either agent alone for achieving steroid-free clinical remission in anti-TNF-naive moderate-to-severe Crohn's disease — 57% in combination vs. 44% infliximab alone vs. 30% azathioprine alone. However, the REACT trial and subsequent guidelines suggest that biologic monotherapy with newer agents (ustekinumab or vedolizumab) is increasingly an option. For anti-TNF-naive patients, infliximab plus an immunomodulator remains preferred to optimize pharmacokinetics (reduce immunogenicity) and efficacy. Ustekinumab is preferred in those with prior TNF failure or TB risk.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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