Drugs for Inflammatory Bowel Disease

Drugs for inflammatory bowel disease induce and maintain remission in ulcerative colitis and Crohn disease, aiming at symptom control, mucosal healing, prevention of complications and avoidance of corticosteroids. Choice depends on disease type, extent, severity, behaviour and risk factors.

Classification. Aminosalicylates, corticosteroids, thiopurines, methotrexate, calcineurin inhibitors, biologics (anti-TNF, anti-integrin, anti-interleukin), small molecule agents (JAK inhibitors, S1P modulators) and antibiotics.

• Mesalazine: induction 2.4 to 4.8 g daily in ulcerative colitis; maintenance 1.6 to 2.4 g daily.
• Prednisolone 40 mg daily for moderate to severe flare, tapered over 8 weeks; budesonide MMX 9 mg daily for 8 weeks in mild to moderate left-sided or extensive colitis, and budesonide 9 mg daily for ileocaecal Crohn disease.
• Azathioprine 2 to 2.5 mg/kg daily; mercaptopurine 1 to 1.5 mg/kg daily; thiopurine methyltransferase activity is checked first.
• Methotrexate 25 mg weekly subcutaneously or intramuscularly for induction in Crohn disease, then 15 mg weekly; folic acid 5 mg weekly.
• Infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, tofacitinib, upadacitinib.

Differences. Mesalazine is effective in ulcerative colitis but not in Crohn disease. Thiopurines and methotrexate are slow, needing 8 to 12 weeks. Biologics act faster and have the best evidence for fistulating disease.

• Mild to moderate ulcerative colitis: rectal and oral mesalazine; add budesonide MMX or prednisolone for non-response.
• Moderate to severe ulcerative colitis: biologic or small molecule agent, with a thiopurine in selected cases.
• Acute severe ulcerative colitis: six or more bloody stools daily plus a heart rate over 90, temperature over 37.8 degrees C, haemoglobin under 10.5 g/dL, or ESR over 30 mm/h. Admit; intravenous methylprednisolone 60 mg daily or hydrocortisone 100 mg four times daily; stool tests for Clostridioides difficile; thromboprophylaxis with low molecular weight heparin. If response is inadequate on day 3 (stool frequency over 8 daily, or 3 to 8 with CRP over 45 mg/L), rescue with infliximab or ciclosporin 2 mg/kg intravenously, or colectomy.
• Crohn disease: budesonide or prednisolone for induction, early biologic therapy for high-risk disease (young, perianal, stricturing, extensive), thiopurine or methotrexate for maintenance; metronidazole and ciprofloxacin for perianal disease.

Selection. Avoid NSAIDs. Smoking worsens Crohn disease.

Contraindications. Active untreated tuberculosis or sepsis for immunosuppressants. Methotrexate and tofacitinib in pregnancy. Live vaccines during immunosuppression.

Adverse effects. Mesalazine: interstitial nephritis. Corticosteroids: hyperglycaemia, osteoporosis, infection. Thiopurines: myelosuppression, hepatotoxicity, pancreatitis, skin cancer, lymphoma. Methotrexate: myelosuppression, hepatotoxicity, pneumonitis. Biologics and small molecules: serious infection, tuberculosis reactivation, hepatitis B reactivation, infusion reactions.

Interactions. Allopurinol with thiopurines requires a 66 to 75 percent dose reduction because of severe myelosuppression. Trimethoprim with methotrexate raises toxicity.

Special groups.

• Pregnancy: mesalazine, thiopurines and anti-TNF drugs are generally continued; methotrexate is contraindicated and tofacitinib is avoided.
• Breastfeeding: mesalazine, thiopurines and anti-TNF drugs acceptable.
• Children: specialist paediatric gastroenterology.
• Older adults: avoid prolonged corticosteroids; higher infection risk.
• Kidney impairment: avoid mesalazine in advanced impairment; reduce methotrexate.
• Regional: before immunosuppression, test for tuberculosis, hepatitis B (HBsAg, anti-HBc), HIV and hepatitis C, and consider strongyloides and schistosomiasis in endemic areas.

Monitoring. Full blood count and liver enzymes every 2 weeks initially for thiopurines and methotrexate, then every 3 months; creatinine yearly for mesalazine; faecal calprotectin and CRP; drug levels for biologics.

Referral and escalation. All new diagnoses need specialist care. Refer urgently for acute severe colitis, toxic megacolon, perforation, obstruction, perianal sepsis, or no response to two lines of therapy; surgical review by day 3 in acute severe colitis.