Drugs for Inflammatory Bowel Disease
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Direct answer
Inflammatory bowel disease therapy steps from aminosalicylates (mesalazine, sulfasalazine) for mild disease, through corticosteroids for induction of remission, to immunomodulators (azathioprine, 6-mercaptopurine, methotrexate) and biologics (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab) for steroid-dependent or refractory disease. Steroids induce remission but never maintain it; thiopurines and biologics maintain steroid-free remission. Topical mesalazine treats ulcerative proctitis and left-sided colitis, Crohn ileitis needs ileal-release budesonide or systemic steroids, and all patients starting immunosuppression need tuberculosis, hepatitis B and Clostridioides difficile screening.
What you must remember
- 5-ASA agents: mesalazine (oral delayed-release or pH-dependent formulations, suppositories for proctitis, enemas for left-sided colitis) inhibits mucosal inflammatory mediators; oral plus topical combined therapy is superior to either alone in ulcerative colitis.
- Sulfasalazine: 5-ASA linked to a sulphapyridine carrier — adverse effects are mostly from the carrier: nausea, headache, rash, haemolysis in G6PD deficiency, reversible oligospermia and orange discolouration of urine and contact lenses; give folic acid supplement.
- Corticosteroids: prednisolone for moderate flares; budesonide with ileal release (Crohn disease) or multimatrix colonic release (ulcerative colitis) limits systemic exposure through first-pass metabolism; steroids are induction-only — no maintenance role.
- Thiopurines: azathioprine and 6-mercaptopurine for steroid-dependent maintenance; check TPMT activity before starting; monitor for myelosuppression, hepatotoxicity, pancreatitis and lymphoma risk; never combine with allopurinol without major dose reduction (xanthine oxidase blocks their clearance).
- Methotrexate: weekly with folic acid for Crohn maintenance, contraindicated in pregnancy and in patients planning conception.
- Biologics: anti-TNF agents infliximab (infusion) and adalimumab and golimumab (subcutaneous) for refractory or fistulising disease; screen for latent tuberculosis and hepatitis B first; vedolizumab (anti-integrin, gut-selective) and ustekinumab (IL-12/23) are alternatives; the JAK inhibitor tofacitinib treats ulcerative colitis with venous thromboembolism and zoster warnings.
- Infection rule: exclude C. difficile and cytomegalovirus infection before escalating immunosuppression for a "refractory" flare.
Common confusion
The classic error is reaching for maintenance steroids — every guideline reserves corticosteroids for induction and mandates steroid-sparing agents for maintenance, because long-term steroids cause toxicity without preventing relapse. Students also confuse the roles of 5-ASA: excellent in ulcerative colitis maintenance, limited value in Crohn disease, where immunomodulators and biologics dominate.
Exam-focused takeaway
Favourite stems include G6PD haemolysis or oligospermia on sulfasalazine, TPMT testing before azathioprine, the catastrophic pancytopenia when allopurinol meets azathioprine, latent tuberculosis screening before anti-TNF therapy, and budesonide as the steroid with minimal systemic effect. Vignettes may describe a young man with perianal fistulising Crohn disease improving on infliximab, or a steroid-dependent patient needing a maintenance agent. Learn maintenance-versus-induction roles first — that single axis organises the entire topic.
Frequently asked questions
Why is sulfasalazine often replaced by mesalazine?
The sulphapyridine carrier causes most toxicity — rash, haemolysis, oligospermia and dyspepsia — so mesalazine delivers the active 5-ASA without it.
Can corticosteroids maintain IBD remission?
No — they induce remission only; maintenance requires 5-ASA, thiopurines, methotrexate or biologics, and chronic steroids cause serious toxicity.
What tests precede anti-TNF therapy?
Screening for latent tuberculosis (chest radiograph with tuberculin or IGRA), hepatitis B serology, and exclusion of active infection or abscess.
Why check TPMT before azathioprine?
TPMT enzyme activity predicts thiopurine clearance — low activity causes drug accumulation with dangerous myelosuppression unless doses are reduced.
Which biologic is gut-selective?
Vedolizumab, an anti-alpha4-beta7 integrin antibody that blocks gut lymphocyte trafficking with little systemic immunosuppression.
What must be excluded before escalating therapy for a refractory ulcerative colitis flare?
Clostridioides difficile and cytomegalovirus infection, which mimic steroid resistance and need specific treatment.